Leptin is a 146-residue secreted four-helix-bundle cytokine-like peptide hormone produced mainly by white adipocytes in proportion to fat mass. Circulating leptin binds the class I cytokine receptor LEPR, assembling ligand-receptor complexes that activate JAK2-STAT3 and other pathways. Its principal physiological role is as the afferent signal of energy stores to the hypothalamus: in the arcuate nucleus it activates anorexigenic POMC neurons and inhibits orexigenic AgRP/NPY neurons, suppressing appetite and supporting energy expenditure. Falling leptin signals starvation and permits the neuroendocrine adaptations to it, so leptin is also required permissively for gonadotropin secretion, puberty and fertility, for thyroid axis activity, and for normal T cell number and function. Peripheral LEPR signalling mediates additional pleiotropic effects on immune cells, endothelium, bone and other tissues. Biallelic loss-of-function LEP variants cause congenital leptin deficiency with severe early-onset hyperphagic obesity, hypogonadotropic hypogonadism and immune dysfunction, all reversed by recombinant leptin (metreleptin).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog-transferred annotation to negative regulation of Pol II transcription. Reason: Leptin is a secreted hormone without nuclear function; transcriptional effects are mediated by LEPR-activated STAT3 in target cells. Leptin acts on this process only indirectly, as an extracellular ligand that activates LEPR-JAK2 signalling in target cells. The annotation is not wrong as a regulatory effect, but it is one of many pleiotropic downstream consequences of receptor activation and does not describe the hormone's own activity. Supporting Evidence: file:human/LEP/LEP-uniprot.txt has central and peripheral effects by binding LEPR PMID:17344214 leptin induced Stat3-phosphorylation-dependent proliferation of MCF7 cells |
| GO:0001525 angiogenesis | IDA PMID:19910644 Leptin enhances the potency of circulating angiogenic cells ... | KEEP AS NON CORE | Summary: Leptin promotes angiogenesis through ObR on endothelial and circulating angiogenic cells. Reason: The experimental data show ObR-dependent pro-angiogenic effects of leptin in vitro and in vivo. This is a genuine peripheral effect of the hormone but not its core energy-homeostasis role. Supporting Evidence: PMID:19910644 These effects required the phosphorylation of alphavbeta5 integrins, which depended on the interaction of leptin with its receptor ObR PMID:11460888 leptin's role as an angiogenesis inducer in the normal organ (rat cornea) |
| GO:0001525 angiogenesis | IDA PMID:21771332 Glioblastoma-derived leptin induces tube formation and growt... | KEEP AS NON CORE | Summary: Leptin promotes angiogenesis through ObR on endothelial and circulating angiogenic cells. Reason: The experimental data show ObR-dependent pro-angiogenic effects of leptin in vitro and in vivo. This is a genuine peripheral effect of the hormone but not its core energy-homeostasis role. Supporting Evidence: PMID:21771332 The mitogenic and angiogenic effects of both CM were blocked by Aca 1, a peptide ObR antagonist PMID:11460888 leptin's role as an angiogenesis inducer in the normal organ (rat cornea) |
| GO:0001542 ovulation from ovarian follicle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ovulation from ovarian follicle, transferred from rodent orthologs. Reason: Leptin is required permissively for reproductive function: leptin restores ovulation in sterile ob/ob females, and leptin therapy permits gonadotropin secretion and puberty in leptin-deficient children. The effect is largely hypothalamic, so it is a non-core, regulatory role. Supporting Evidence: PMID:8589726 repeated administration of only the recombinant human ob protein, leptin, into homozygous female ob/ob mice can correct their sterility, thus resulting in ovulation, pregnancy and parturition PMID:12393845 through its age-dependent effects on gonadotropin secretion, facilitated appropriately timed pubertal development |
| GO:0001666 response to hypoxia | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog-transferred 'response to hypoxia' annotation. Reason: This is an ortholog-transferred (Ensembl Compara) annotation that most plausibly reflects regulation of leptin gene expression or circulating leptin levels by this stimulus in rodents, not a function performed by the leptin protein. Leptin is a secreted hormone whose function is to signal through LEPR. Supporting Evidence: PMID:9054940 Leptin is a serum protein which is secreted by adipocytes and thought to play a role in the regulation of body fat. file:human/LEP/LEP-uniprot.txt Key player in the regulation of energy balance and body weight control. |
| GO:0001819 positive regulation of cytokine production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Leptin increases production of pro-inflammatory cytokines in several cell types. Reason: Supported for human cartilage (IL-6, IL-8) and immune cells. A genuine pleiotropic effect of LEPR activation, not the core function. Supporting Evidence: PMID:19688109 Leptin alone or in combination with IL-1 enhanced the expression of iNOS and COX-2, and production of NO, PGE(2), IL-6, and IL-8. PMID:12393845 Leptin deficiency was associated with reduced numbers of circulating CD4(+) T cells and impaired T cell proliferation and cytokine release |
| GO:0001890 placenta development | IDA PMID:17957153 Milk intake and feeding behavior in the first week of life a... | UNDECIDED | Summary: Placenta development from a cord-blood feeding-behaviour study. Reason: The cached abstract of PMID:17957153 concerns cord blood leptin and neonatal milk intake and reports no relationship between cord leptin and feeding; it does not mention placental development. Full text is not available to us, so the basis for this IDA cannot be verified. Supporting Evidence: PMID:17957153 Total cord ghrelin and leptin are not directly related to milk intake or feed frequency in the first week of life. |
| GO:0001936 regulation of endothelial cell proliferation | IDA PMID:11460888 Potential role of leptin in angiogenesis: leptin induces end... | KEEP AS NON CORE | Summary: Leptin induces endothelial cell proliferation. Reason: Experimental support for a mitogenic effect of leptin on vascular endothelial cells via ObR; a peripheral, non-core effect. Supporting Evidence: PMID:11460888 Leptin (10-40 ng/ml) induced proliferation of the human umbilical vein endothelial cells (HUVECs) |
| GO:0002021 response to dietary excess | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog-transferred 'response to dietary excess' annotation. Reason: This is an ortholog-transferred (Ensembl Compara) annotation that most plausibly reflects regulation of leptin gene expression or circulating leptin levels by this stimulus in rodents, not a function performed by the leptin protein. Leptin is a secreted hormone whose function is to signal through LEPR. Supporting Evidence: PMID:9054940 Leptin is a serum protein which is secreted by adipocytes and thought to play a role in the regulation of body fat. file:human/LEP/LEP-uniprot.txt Key player in the regulation of energy balance and body weight control. |
| GO:0003300 cardiac muscle hypertrophy | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Cardiac muscle hypertrophy transferred from rat. Reason: Leptin may promote cardiomyocyte hypertrophy via LEPR in rodent models, but it does not carry out hypertrophic growth itself. Leptin acts on this process only indirectly, as an extracellular ligand that activates LEPR-JAK2 signalling in target cells. The annotation is not wrong as a regulatory effect, but it is one of many pleiotropic downstream consequences of receptor activation and does not describe the hormone's own activity. Supporting Evidence: file:human/LEP/LEP-uniprot.txt has central and peripheral effects by binding LEPR |
| GO:0003677 DNA binding | IEA GO_REF:0000107 | REMOVE | Summary: DNA binding transferred from mouse ortholog. Reason: Leptin is a signal-peptide-containing secreted four-helix cytokine-like hormone with no DNA-binding domain and no nuclear localisation; a DNA-binding molecular function is not supported for the leptin protein. Supporting Evidence: file:human/LEP/LEP-uniprot.txt FT SIGNAL 1..21 file:human/LEP/LEP-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0005102 signaling receptor binding | IEA GO_REF:0000107 | MODIFY | Summary: Signaling receptor binding transferred from rat ortholog. Reason: Correct but uninformative; leptin's receptor is LEPR and the specific term leptin receptor binding is available and experimentally supported. Proposed replacements: leptin receptor binding Supporting Evidence: file:human/LEP/LEP-uniprot.txt has central and peripheral effects by binding LEPR PMID:36959263 Leptin activates its receptor LEP-R in the hypothalamus to regulate body weight |
| GO:0005179 hormone activity | IBA GO_REF:0000033 | ACCEPT | Summary: Hormone activity (IBA). Reason: Leptin is the adipocyte-derived circulating hormone that signals body fat stores to the brain; hormone activity is its defining molecular function. Supporting Evidence: PMID:7624777 These data suggest that the OB protein serves an endocrine function to regulate body fat stores. PMID:27037668 The adipocyte-derived hormone leptin regulates appetite and energy homeostasis through the activation of leptin receptors (ObR) on hypothalamic neurones PMID:9202122 The severe obesity found in these congenitally leptin-deficient subjects provides the first genetic evidence that leptin is an important regulator of energy balance in humans. |
| GO:0005179 hormone activity | IDA PMID:27037668 Inhibition of Leptin-ObR Interaction Does not Prevent Leptin... | ACCEPT | Summary: Hormone activity (IDA). Reason: Leptin is the adipocyte-derived circulating hormone that signals body fat stores to the brain; hormone activity is its defining molecular function. Supporting Evidence: PMID:7624777 These data suggest that the OB protein serves an endocrine function to regulate body fat stores. PMID:27037668 The adipocyte-derived hormone leptin regulates appetite and energy homeostasis through the activation of leptin receptors (ObR) on hypothalamic neurones PMID:9202122 The severe obesity found in these congenitally leptin-deficient subjects provides the first genetic evidence that leptin is an important regulator of energy balance in humans. |
| GO:0005179 hormone activity | IEA GO_REF:0000120 | ACCEPT | Summary: Hormone activity (IEA). Reason: Leptin is the adipocyte-derived circulating hormone that signals body fat stores to the brain; hormone activity is its defining molecular function. Supporting Evidence: PMID:7624777 These data suggest that the OB protein serves an endocrine function to regulate body fat stores. PMID:27037668 The adipocyte-derived hormone leptin regulates appetite and energy homeostasis through the activation of leptin receptors (ObR) on hypothalamic neurones PMID:9202122 The severe obesity found in these congenitally leptin-deficient subjects provides the first genetic evidence that leptin is an important regulator of energy balance in humans. |
| GO:0005179 hormone activity | ISS GO_REF:0000024 | ACCEPT | Summary: Hormone activity (ISS). Reason: Leptin is the adipocyte-derived circulating hormone that signals body fat stores to the brain; hormone activity is its defining molecular function. Supporting Evidence: PMID:7624777 These data suggest that the OB protein serves an endocrine function to regulate body fat stores. PMID:27037668 The adipocyte-derived hormone leptin regulates appetite and energy homeostasis through the activation of leptin receptors (ObR) on hypothalamic neurones PMID:9202122 The severe obesity found in these congenitally leptin-deficient subjects provides the first genetic evidence that leptin is an important regulator of energy balance in humans. |
| GO:0005515 protein binding | IPI PMID:22405007 Structure of the human obesity receptor leptin-binding domai... | MODIFY | Summary: Protein binding with LEPR (P48357). Reason: The interaction partner is the leptin receptor; 'protein binding' is uninformative and should be replaced by leptin receptor binding. Proposed replacements: leptin receptor binding Supporting Evidence: PMID:22405007 A molecular model of the putative leptin-LBD complex reveals that 9F8 Fab blocks leptin binding file:human/LEP/LEP-uniprot.txt has central and peripheral effects by binding LEPR |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding with HSF2BP (high-throughput binary interactome). Reason: A screen-derived binary interaction with no established physiological role for leptin; 'protein binding' adds no functional information and no more informative function is supported by the screen. Removal does not imply the interaction is false. The physiological binding partner of leptin is LEPR. Supporting Evidence: file:human/LEP/LEP-uniprot.txt has central and peripheral effects by binding LEPR |
| GO:0005515 protein binding | IPI PMID:32822567 A Human IgSF Cell-Surface Interactome Reveals a Complex Netw... | MODIFY | Summary: Protein binding with LEPR (P48357). Reason: The interaction partner is the leptin receptor; 'protein binding' is uninformative and should be replaced by leptin receptor binding. Proposed replacements: leptin receptor binding Supporting Evidence: PMID:36959263 Leptin induces type I cytokine receptor assemblies featuring 3:3 stoichiometry file:human/LEP/LEP-uniprot.txt has central and peripheral effects by binding LEPR |
| GO:0005515 protein binding | IPI PMID:32822567 A Human IgSF Cell-Surface Interactome Reveals a Complex Netw... | REMOVE | Summary: Protein binding with mouse Islr2 (IgSF cell-surface interactome). Reason: A screen-derived binary interaction with no established physiological role for leptin; 'protein binding' adds no functional information and no more informative function is supported by the screen. Removal does not imply the interaction is false. The physiological binding partner of leptin is LEPR. Supporting Evidence: file:human/LEP/LEP-uniprot.txt has central and peripheral effects by binding LEPR |
| GO:0005515 protein binding | IPI PMID:32822567 A Human IgSF Cell-Surface Interactome Reveals a Complex Netw... | REMOVE | Summary: Protein binding with ISLR2 (IgSF cell-surface interactome). Reason: A screen-derived binary interaction with no established physiological role for leptin; 'protein binding' adds no functional information and no more informative function is supported by the screen. Removal does not imply the interaction is false. The physiological binding partner of leptin is LEPR. Supporting Evidence: file:human/LEP/LEP-uniprot.txt has central and peripheral effects by binding LEPR |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Protein binding with LEPR (P48357). Reason: The interaction partner is the leptin receptor; 'protein binding' is uninformative and should be replaced by leptin receptor binding. Proposed replacements: leptin receptor binding Supporting Evidence: PMID:36959263 Leptin induces type I cytokine receptor assemblies featuring 3:3 stoichiometry file:human/LEP/LEP-uniprot.txt has central and peripheral effects by binding LEPR |
| GO:0005576 extracellular region | IBA GO_REF:0000033 | ACCEPT | Summary: Extracellular region (IBA). Reason: Leptin is secreted from adipocytes into the circulation and acts as an endocrine signal; extracellular localisation is correct. Supporting Evidence: PMID:7624777 The ob product was shown to be present as a 16-kilodalton protein in mouse and human plasma file:human/LEP/LEP-uniprot.txt SUBCELLULAR LOCATION: Secreted PMID:9054940 Leptin is a serum protein which is secreted by adipocytes and thought to play a role in the regulation of body fat. |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | ACCEPT | Summary: Extracellular region (IEA). Reason: Leptin is secreted from adipocytes into the circulation and acts as an endocrine signal; extracellular localisation is correct. Supporting Evidence: PMID:7624777 The ob product was shown to be present as a 16-kilodalton protein in mouse and human plasma file:human/LEP/LEP-uniprot.txt SUBCELLULAR LOCATION: Secreted PMID:9054940 Leptin is a serum protein which is secreted by adipocytes and thought to play a role in the regulation of body fat. |
| GO:0005576 extracellular region | ISS GO_REF:0000024 | ACCEPT | Summary: Extracellular region (ISS). Reason: Leptin is secreted from adipocytes into the circulation and acts as an endocrine signal; extracellular localisation is correct. Supporting Evidence: PMID:7624777 The ob product was shown to be present as a 16-kilodalton protein in mouse and human plasma file:human/LEP/LEP-uniprot.txt SUBCELLULAR LOCATION: Secreted PMID:9054940 Leptin is a serum protein which is secreted by adipocytes and thought to play a role in the regulation of body fat. |
| GO:0005576 extracellular region | TAS PMID:9054940 A major quantitative trait locus determining serum leptin le... | ACCEPT | Summary: Extracellular region (TAS). Reason: Leptin is secreted from adipocytes into the circulation and acts as an endocrine signal; extracellular localisation is correct. Supporting Evidence: PMID:7624777 The ob product was shown to be present as a 16-kilodalton protein in mouse and human plasma file:human/LEP/LEP-uniprot.txt SUBCELLULAR LOCATION: Secreted PMID:9054940 Leptin is a serum protein which is secreted by adipocytes and thought to play a role in the regulation of body fat. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1183003 | ACCEPT | Summary: Extracellular region (TAS). Reason: Leptin is secreted from adipocytes into the circulation and acts as an endocrine signal; extracellular localisation is correct. Supporting Evidence: PMID:7624777 The ob product was shown to be present as a 16-kilodalton protein in mouse and human plasma file:human/LEP/LEP-uniprot.txt SUBCELLULAR LOCATION: Secreted PMID:9054940 Leptin is a serum protein which is secreted by adipocytes and thought to play a role in the regulation of body fat. Reactome:R-HSA-1183003 The Ob gene encoding leptin is transcribed to yield mRNA and translated to yield protein. |
| GO:0005737 cytoplasm | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Cytoplasm transferred from mouse. Reason: Leptin transits the secretory pathway after signal-peptide cleavage and is secreted; a generic cytoplasm location is not informative for the mature hormone, whose functional location is extracellular. Supporting Evidence: file:human/LEP/LEP-uniprot.txt FT SIGNAL 1..21 file:human/LEP/LEP-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0005829 cytosol | IEA GO_REF:0000107 | REMOVE | Summary: Cytosol, transferred from rat ortholog. Reason: Leptin carries an N-terminal signal peptide and is co-translationally targeted to the secretory pathway and secreted; it is not a cytosolic protein. A cytosolic location is inconsistent with its biogenesis and function. Supporting Evidence: file:human/LEP/LEP-uniprot.txt FT SIGNAL 1..21 file:human/LEP/LEP-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0005829 cytosol | ISS GO_REF:0000024 | REMOVE | Summary: Cytosol, transferred from rat ortholog. Reason: Leptin carries an N-terminal signal peptide and is co-translationally targeted to the secretory pathway and secreted; it is not a cytosolic protein. A cytosolic location is inconsistent with its biogenesis and function. Supporting Evidence: file:human/LEP/LEP-uniprot.txt FT SIGNAL 1..21 file:human/LEP/LEP-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0006112 energy reserve metabolic process | IBA GO_REF:0000033 | MODIFY | Summary: Energy reserve metabolic process (IBA). Reason: Leptin does not itself catalyse or perform storage or mobilisation of energy reserves; it regulates them systemically by signalling adipose mass to the hypothalamus. The appropriate process is energy homeostasis. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN002620302 SUPPORTS TRANSFER Leptin family node; the conserved ancestral role is endocrine regulation of energy stores, which is better captured by energy homeostasis than by a metabolic-process term. RGD:3000 SUPPORTS TRANSFER Rodent leptin ortholog; the underlying biology (leptin regulating this process or being regulated by it) is conserved, but the term conflates regulation with participation. Proposed replacements: energy homeostasis Supporting Evidence: PMID:7624777 These data suggest that the OB protein serves an endocrine function to regulate body fat stores. PMID:9202122 The severe obesity found in these congenitally leptin-deficient subjects provides the first genetic evidence that leptin is an important regulator of energy balance in humans. |
| GO:0006112 energy reserve metabolic process | IEA GO_REF:0000107 | MODIFY | Summary: Energy reserve metabolic process (IEA). Reason: Leptin does not itself catalyse or perform storage or mobilisation of energy reserves; it regulates them systemically by signalling adipose mass to the hypothalamus. The appropriate process is energy homeostasis. Proposed replacements: energy homeostasis Supporting Evidence: PMID:7624777 These data suggest that the OB protein serves an endocrine function to regulate body fat stores. PMID:9202122 The severe obesity found in these congenitally leptin-deficient subjects provides the first genetic evidence that leptin is an important regulator of energy balance in humans. |
| GO:0006112 energy reserve metabolic process | TAS PMID:9537324 A mutation in the human leptin receptor gene causes obesity ... | MODIFY | Summary: Energy reserve metabolic process (TAS). Reason: Leptin does not itself catalyse or perform storage or mobilisation of energy reserves; it regulates them systemically by signalling adipose mass to the hypothalamus. The appropriate process is energy homeostasis. Proposed replacements: energy homeostasis Supporting Evidence: PMID:9537324 The adipocyte-specific hormone leptin, the product of the obese (ob) gene, regulates adipose-tissue mass through hypothalamic effects on satiety and energy expenditure. PMID:9202122 The severe obesity found in these congenitally leptin-deficient subjects provides the first genetic evidence that leptin is an important regulator of energy balance in humans. |
| GO:0006114 glycerol biosynthetic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Glycerol biosynthetic process transferred from rat. Reason: Leptin is a hormone and does not participate in glycerol biosynthesis; any effect on glycerol metabolism is indirect. Leptin acts on this process only indirectly, as an extracellular ligand that activates LEPR-JAK2 signalling in target cells. The annotation is not wrong as a regulatory effect, but it is one of many pleiotropic downstream consequences of receptor activation and does not describe the hormone's own activity. Supporting Evidence: file:human/LEP/LEP-uniprot.txt Key player in the regulation of energy balance and body weight control. |
| GO:0006629 lipid metabolic process | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Lipid metabolic process (IBA). Reason: Leptin regulates body fat stores and lipid metabolism indirectly through central and peripheral LEPR signalling; it is not a participant in lipid metabolic reactions. The core process is energy homeostasis. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN002620302 SUPPORTS TRANSFER Leptin family node; lipid metabolism is regulated indirectly by leptin signalling rather than performed by the hormone. MGI:MGI:104663 SUPPORTS TRANSFER Rodent leptin ortholog; the underlying biology (leptin regulating this process or being regulated by it) is conserved, but the term conflates regulation with participation. RGD:3000 SUPPORTS TRANSFER Rodent leptin ortholog; the underlying biology (leptin regulating this process or being regulated by it) is conserved, but the term conflates regulation with participation. Supporting Evidence: PMID:7624777 These data suggest that the OB protein serves an endocrine function to regulate body fat stores. |
| GO:0006909 phagocytosis | IEA GO_REF:0000120 | MARK AS OVER ANNOTATED | Summary: Phagocytosis (ARBA/IEA). Reason: UniProt notes leptin increases phagocytosis by macrophages, i.e. a regulatory effect on immune cells via LEPR; the hormone does not perform phagocytosis. Supporting Evidence: file:human/LEP/LEP-uniprot.txt Increases phagocytosis by macrophages and enhances secretion of pro-inflammatory mediators. |
| GO:0007165 signal transduction | IEA GO_REF:0000002 | MODIFY | Summary: Signal transduction (InterPro2GO). Reason: Correct but very general. Leptin acts as the ligand of the leptin-mediated signaling pathway. Proposed replacements: leptin-mediated signaling pathway Supporting Evidence: PMID:27037668 The adipocyte-derived hormone leptin regulates appetite and energy homeostasis through the activation of leptin receptors (ObR) on hypothalamic neurones PMID:36959263 Leptin activates its receptor LEP-R in the hypothalamus to regulate body weight |
| GO:0007259 cell surface receptor signaling pathway via JAK-STAT | IEA GO_REF:0000107 | MODIFY | Summary: Cell surface receptor signaling pathway via JAK-STAT (IEA). Reason: Leptin activates LEPR-JAK2-STAT3; the specific GO term leptin-mediated signaling pathway describes the pathway initiated by this ligand. Proposed replacements: leptin-mediated signaling pathway Supporting Evidence: PMID:17344214 leptin induced Stat3-phosphorylation-dependent proliferation of MCF7 cells PMID:27037668 The adipocyte-derived hormone leptin regulates appetite and energy homeostasis through the activation of leptin receptors (ObR) on hypothalamic neurones |
| GO:0007565 female pregnancy | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Female pregnancy, transferred from rat. Reason: Leptin is permissive for female reproduction: leptin treatment restores ovulation, pregnancy and parturition in ob/ob females. A non-core role. Supporting Evidence: PMID:8589726 repeated administration of only the recombinant human ob protein, leptin, into homozygous female ob/ob mice can correct their sterility, thus resulting in ovulation, pregnancy and parturition |
| GO:0007584 response to nutrient | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog-transferred 'response to nutrient' annotation. Reason: This is an ortholog-transferred (Ensembl Compara) annotation that most plausibly reflects regulation of leptin gene expression or circulating leptin levels by this stimulus in rodents, not a function performed by the leptin protein. Leptin is a secreted hormone whose function is to signal through LEPR. Supporting Evidence: PMID:9054940 Leptin is a serum protein which is secreted by adipocytes and thought to play a role in the regulation of body fat. file:human/LEP/LEP-uniprot.txt Key player in the regulation of energy balance and body weight control. |
| GO:0007623 circadian rhythm | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Circadian rhythm transferred from rat. Reason: Circulating leptin shows diurnal variation, which reflects regulation of leptin secretion rather than participation of leptin in the circadian clock. This is an ortholog-transferred (Ensembl Compara) annotation that most plausibly reflects regulation of leptin gene expression or circulating leptin levels by this stimulus in rodents, not a function performed by the leptin protein. Leptin is a secreted hormone whose function is to signal through LEPR. Supporting Evidence: PMID:9054940 Leptin is a serum protein which is secreted by adipocytes and thought to play a role in the regulation of body fat. |
| GO:0008217 regulation of blood pressure | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Regulation of blood pressure transferred from rat. Reason: Leptin acts on this process only indirectly, as an extracellular ligand that activates LEPR-JAK2 signalling in target cells. The annotation is not wrong as a regulatory effect, but it is one of many pleiotropic downstream consequences of receptor activation and does not describe the hormone's own activity. Supporting Evidence: PMID:28270795 However, this adipocyte-derived hormone also directs peripheral processes, including immunity, reproduction, and bone metabolism. |
| GO:0008284 positive regulation of cell population proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of cell population proliferation. Reason: Leptin is mitogenic for several LEPR-expressing cell types (endothelial cells, breast cancer cells). A real but non-core effect. Supporting Evidence: PMID:17344214 Leptin increased MCF7 cell population in the S-phase of the cell cycle along with a robust increase in CYCLIN D1 expression. PMID:11460888 Leptin (10-40 ng/ml) induced proliferation of the human umbilical vein endothelial cells (HUVECs) |
| GO:0008343 adult feeding behavior | IEA GO_REF:0000107 | MODIFY | Summary: Adult feeding behavior (ortholog transfer). Reason: Leptin restrains food intake; the more precise GO process is negative regulation of appetite by leptin-mediated signaling pathway. Proposed replacements: negative regulation of appetite by leptin-mediated signaling pathway Supporting Evidence: PMID:7624777 The protein reduced food intake and increased energy expenditure in ob/ob mice. PMID:12393845 with sustained, beneficial effects on appetite, fat mass, hyperinsulinemia, and hyperlipidemia |
| GO:0008343 adult feeding behavior | ISS GO_REF:0000024 | MODIFY | Summary: Adult feeding behavior (ortholog transfer). Reason: Leptin restrains food intake; the more precise GO process is negative regulation of appetite by leptin-mediated signaling pathway. Proposed replacements: negative regulation of appetite by leptin-mediated signaling pathway Supporting Evidence: PMID:7624777 The protein reduced food intake and increased energy expenditure in ob/ob mice. PMID:12393845 with sustained, beneficial effects on appetite, fat mass, hyperinsulinemia, and hyperlipidemia |
| GO:0009062 fatty acid catabolic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Fatty acid catabolic process transferred from rat. Reason: Leptin acts on this process only indirectly, as an extracellular ligand that activates LEPR-JAK2 signalling in target cells. The annotation is not wrong as a regulatory effect, but it is one of many pleiotropic downstream consequences of receptor activation and does not describe the hormone's own activity. Supporting Evidence: file:human/LEP/LEP-uniprot.txt In the periphery, increases basal metabolism, influences reproductive function, regulates pancreatic beta-cell function and insulin secretion |
| GO:0010507 negative regulation of autophagy | IDA PMID:25060689 Leptin modulates autophagy in human CD4+CD25- conventional T... | KEEP AS NON CORE | Summary: Negative regulation of autophagy in T cells. Reason: Leptin inhibits autophagy in human CD4+CD25- T cells during TCR stimulation via mTOR. A genuine immunometabolic effect, but not leptin's core function. Supporting Evidence: PMID:25060689 In vitro treatment with recombinant human leptin determined an inhibition of autophagy during T cell receptor (TCR) stimulation |
| GO:0010507 negative regulation of autophagy | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of autophagy in T cells. Reason: Leptin inhibits autophagy in human CD4+CD25- T cells during TCR stimulation via mTOR. A genuine immunometabolic effect, but not leptin's core function. Supporting Evidence: PMID:25060689 In vitro treatment with recombinant human leptin determined an inhibition of autophagy during T cell receptor (TCR) stimulation |
| GO:0010888 negative regulation of lipid storage | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of lipid storage (rat ortholog transfer). Reason: Leptin administration reduces body fat stores, and leptin deficiency causes massive fat accumulation. This is a systemic consequence of the core energy-homeostasis function. Supporting Evidence: PMID:7624777 These data suggest that the OB protein serves an endocrine function to regulate body fat stores. PMID:9202122 The severe obesity found in these congenitally leptin-deficient subjects provides the first genetic evidence that leptin is an important regulator of energy balance in humans. |
| GO:0014823 response to activity | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog-transferred 'response to activity' annotation. Reason: This is an ortholog-transferred (Ensembl Compara) annotation that most plausibly reflects regulation of leptin gene expression or circulating leptin levels by this stimulus in rodents, not a function performed by the leptin protein. Leptin is a secreted hormone whose function is to signal through LEPR. Supporting Evidence: PMID:9054940 Leptin is a serum protein which is secreted by adipocytes and thought to play a role in the regulation of body fat. file:human/LEP/LEP-uniprot.txt Key player in the regulation of energy balance and body weight control. |
| GO:0019953 sexual reproduction | IMP PMID:8589726 Correction of the sterility defect in homozygous obese femal... | KEEP AS NON CORE | Summary: Sexual reproduction (IMP, ob/ob mouse). Reason: Leptin treatment corrects the sterility of ob/ob female mice, and leptin is required for pubertal gonadotropin secretion in humans. A non-core neuroendocrine role. Supporting Evidence: PMID:8589726 repeated administration of only the recombinant human ob protein, leptin, into homozygous female ob/ob mice can correct their sterility, thus resulting in ovulation, pregnancy and parturition PMID:12393845 through its age-dependent effects on gonadotropin secretion, facilitated appropriately timed pubertal development |
| GO:0030217 T cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: T cell differentiation (ortholog transfer). Reason: Leptin deficiency in humans reduces CD4+ T cell numbers and T cell responses, reversed by leptin therapy; a non-core immune role. Supporting Evidence: PMID:12393845 Leptin deficiency was associated with reduced numbers of circulating CD4(+) T cells and impaired T cell proliferation and cytokine release |
| GO:0030217 T cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: T cell differentiation (ortholog transfer). Reason: Leptin deficiency in humans reduces CD4+ T cell numbers and T cell responses, reversed by leptin therapy; a non-core immune role. Supporting Evidence: PMID:12393845 Leptin deficiency was associated with reduced numbers of circulating CD4(+) T cells and impaired T cell proliferation and cytokine release |
| GO:0031667 response to nutrient levels | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog-transferred 'response to nutrient levels' annotation. Reason: This is an ortholog-transferred (Ensembl Compara) annotation that most plausibly reflects regulation of leptin gene expression or circulating leptin levels by this stimulus in rodents, not a function performed by the leptin protein. Leptin is a secreted hormone whose function is to signal through LEPR. Supporting Evidence: PMID:9054940 Leptin is a serum protein which is secreted by adipocytes and thought to play a role in the regulation of body fat. file:human/LEP/LEP-uniprot.txt Key player in the regulation of energy balance and body weight control. |
| GO:0032008 positive regulation of TOR signaling | IDA PMID:25060689 Leptin modulates autophagy in human CD4+CD25- conventional T... | KEEP AS NON CORE | Summary: Positive regulation of TOR signaling in T cells. Reason: Leptin activates mTOR in human conventional T cells during TCR stimulation; downstream of LEPR, non-core. Supporting Evidence: PMID:25060689 The events were secondary to the activation of the mammalian-target of rapamycin |
| GO:0032099 negative regulation of appetite | IEA GO_REF:0000107 | ACCEPT | Summary: Negative regulation of appetite (IEA). Reason: Suppression of appetite is a central function of leptin, shown by leptin's effect on food intake in ob/ob mice and in leptin-deficient humans. Supporting Evidence: PMID:7624777 The protein reduced food intake and increased energy expenditure in ob/ob mice. PMID:12393845 with sustained, beneficial effects on appetite, fat mass, hyperinsulinemia, and hyperlipidemia |
| GO:0032099 negative regulation of appetite | ISS GO_REF:0000024 | ACCEPT | Summary: Negative regulation of appetite (ISS). Reason: Suppression of appetite is a central function of leptin, shown by leptin's effect on food intake in ob/ob mice and in leptin-deficient humans. Supporting Evidence: PMID:7624777 The protein reduced food intake and increased energy expenditure in ob/ob mice. PMID:12393845 with sustained, beneficial effects on appetite, fat mass, hyperinsulinemia, and hyperlipidemia |
| GO:0032310 prostaglandin secretion | IDA PMID:19688109 Leptin enhances synthesis of proinflammatory mediators in hu... | MODIFY | Summary: Prostaglandin secretion (IDA, human OA cartilage). Reason: Leptin increased PGE2 production by chondrocytes; leptin is the stimulus rather than a participant in prostaglandin secretion, so a positive-regulation term is more accurate. Proposed replacements: positive regulation of prostaglandin secretion Supporting Evidence: PMID:19688109 Leptin alone or in combination with IL-1 enhanced the expression of iNOS and COX-2, and production of NO, PGE(2), IL-6, and IL-8. |
| GO:0032355 response to estradiol | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog-transferred 'response to estradiol' annotation. Reason: This is an ortholog-transferred (Ensembl Compara) annotation that most plausibly reflects regulation of leptin gene expression or circulating leptin levels by this stimulus in rodents, not a function performed by the leptin protein. Leptin is a secreted hormone whose function is to signal through LEPR. Supporting Evidence: PMID:9054940 Leptin is a serum protein which is secreted by adipocytes and thought to play a role in the regulation of body fat. file:human/LEP/LEP-uniprot.txt Key player in the regulation of energy balance and body weight control. |
| GO:0032735 positive regulation of interleukin-12 production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of IL-12 production (mouse ortholog). Reason: Leptin is pro-inflammatory and promotes Th1-type cytokine production; non-core. Supporting Evidence: file:human/LEP/LEP-uniprot.txt Increases phagocytosis by macrophages and enhances secretion of pro-inflammatory mediators. |
| GO:0032755 positive regulation of interleukin-6 production | IDA PMID:19688109 Leptin enhances synthesis of proinflammatory mediators in hu... | KEEP AS NON CORE | Summary: Leptin increases IL-6/IL-8 production. Reason: Experimentally supported in human osteoarthritic cartilage; a peripheral pro-inflammatory effect via LEPR. Supporting Evidence: PMID:19688109 Leptin alone or in combination with IL-1 enhanced the expression of iNOS and COX-2, and production of NO, PGE(2), IL-6, and IL-8. |
| GO:0032755 positive regulation of interleukin-6 production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Leptin increases IL-6/IL-8 production. Reason: Experimentally supported in human osteoarthritic cartilage; a peripheral pro-inflammatory effect via LEPR. Supporting Evidence: PMID:19688109 Leptin alone or in combination with IL-1 enhanced the expression of iNOS and COX-2, and production of NO, PGE(2), IL-6, and IL-8. |
| GO:0032757 positive regulation of interleukin-8 production | IDA PMID:19688109 Leptin enhances synthesis of proinflammatory mediators in hu... | KEEP AS NON CORE | Summary: Leptin increases IL-6/IL-8 production. Reason: Experimentally supported in human osteoarthritic cartilage; a peripheral pro-inflammatory effect via LEPR. Supporting Evidence: PMID:19688109 Leptin alone or in combination with IL-1 enhanced the expression of iNOS and COX-2, and production of NO, PGE(2), IL-6, and IL-8. |
| GO:0032760 positive regulation of tumor necrosis factor production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of TNF production (mouse ortholog). Reason: Consistent with leptin's pro-inflammatory effects on macrophages; non-core. Supporting Evidence: file:human/LEP/LEP-uniprot.txt Increases phagocytosis by macrophages and enhances secretion of pro-inflammatory mediators. |
| GO:0032814 regulation of natural killer cell activation | IDA PMID:12504075 Expression of leptin receptors and response to leptin stimul... | KEEP AS NON CORE | Summary: Leptin regulates NK cell proliferation and cytotoxicity. Reason: Human NK cell lines express LEPR and respond to leptin with STAT3 activation, proliferation and increased cytotoxicity; a non-core immune effect. Supporting Evidence: PMID:12504075 The IL-2-independent YT cells were dose-dependently responsible for leptin stimulation to manifest rapid proliferation and strong cytotoxicity against tumor targets. |
| GO:0032817 regulation of natural killer cell proliferation | IDA PMID:12504075 Expression of leptin receptors and response to leptin stimul... | KEEP AS NON CORE | Summary: Leptin regulates NK cell proliferation and cytotoxicity. Reason: Human NK cell lines express LEPR and respond to leptin with STAT3 activation, proliferation and increased cytotoxicity; a non-core immune effect. Supporting Evidence: PMID:12504075 The IL-2-independent YT cells were dose-dependently responsible for leptin stimulation to manifest rapid proliferation and strong cytotoxicity against tumor targets. |
| GO:0032868 response to insulin | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Response to insulin (IBA). Reason: Insulin stimulates leptin synthesis and secretion by adipocytes, so this reflects regulation of LEP expression rather than a function of leptin. This is an ortholog-transferred (Ensembl Compara) annotation that most plausibly reflects regulation of leptin gene expression or circulating leptin levels by this stimulus in rodents, not a function performed by the leptin protein. Leptin is a secreted hormone whose function is to signal through LEPR. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN002620302 SUPPORTS TRANSFER Leptin family node; insulin regulates leptin expression and secretion, so 'response to insulin' describes regulation of the gene rather than a leptin function. MGI:MGI:104663 SUPPORTS TRANSFER Rodent leptin ortholog; the underlying biology (leptin regulating this process or being regulated by it) is conserved, but the term conflates regulation with participation. Supporting Evidence: PMID:9054940 Leptin is a serum protein which is secreted by adipocytes and thought to play a role in the regulation of body fat. |
| GO:0033197 response to vitamin E | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog-transferred 'response to vitamin E' annotation. Reason: This is an ortholog-transferred (Ensembl Compara) annotation that most plausibly reflects regulation of leptin gene expression or circulating leptin levels by this stimulus in rodents, not a function performed by the leptin protein. Leptin is a secreted hormone whose function is to signal through LEPR. Supporting Evidence: PMID:9054940 Leptin is a serum protein which is secreted by adipocytes and thought to play a role in the regulation of body fat. file:human/LEP/LEP-uniprot.txt Key player in the regulation of energy balance and body weight control. |
| GO:0033210 leptin-mediated signaling pathway | IDA PMID:27037668 Inhibition of Leptin-ObR Interaction Does not Prevent Leptin... | ACCEPT | Summary: Leptin-mediated signaling pathway (IDA). Reason: Leptin is the ligand that initiates the leptin-mediated signaling pathway by binding and assembling LEPR complexes on hypothalamic and peripheral target cells. Supporting Evidence: PMID:27037668 The adipocyte-derived hormone leptin regulates appetite and energy homeostasis through the activation of leptin receptors (ObR) on hypothalamic neurones PMID:36959263 Leptin induces type I cytokine receptor assemblies featuring 3:3 stoichiometry |
| GO:0033210 leptin-mediated signaling pathway | IEA GO_REF:0000120 | ACCEPT | Summary: Leptin-mediated signaling pathway (IEA). Reason: Leptin is the ligand that initiates the leptin-mediated signaling pathway by binding and assembling LEPR complexes on hypothalamic and peripheral target cells. Supporting Evidence: PMID:27037668 The adipocyte-derived hormone leptin regulates appetite and energy homeostasis through the activation of leptin receptors (ObR) on hypothalamic neurones PMID:36959263 Leptin induces type I cytokine receptor assemblies featuring 3:3 stoichiometry |
| GO:0033210 leptin-mediated signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: Leptin-mediated signaling pathway (ISS). Reason: Leptin is the ligand that initiates the leptin-mediated signaling pathway by binding and assembling LEPR complexes on hypothalamic and peripheral target cells. Supporting Evidence: PMID:27037668 The adipocyte-derived hormone leptin regulates appetite and energy homeostasis through the activation of leptin receptors (ObR) on hypothalamic neurones PMID:36959263 Leptin induces type I cytokine receptor assemblies featuring 3:3 stoichiometry |
| GO:0033210 leptin-mediated signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: Leptin-mediated signaling pathway (ISS). Reason: Leptin is the ligand that initiates the leptin-mediated signaling pathway by binding and assembling LEPR complexes on hypothalamic and peripheral target cells. Supporting Evidence: PMID:27037668 The adipocyte-derived hormone leptin regulates appetite and energy homeostasis through the activation of leptin receptors (ObR) on hypothalamic neurones PMID:36959263 Leptin induces type I cytokine receptor assemblies featuring 3:3 stoichiometry |
| GO:0033686 positive regulation of luteinizing hormone secretion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of luteinizing hormone secretion (rat ortholog). Reason: Leptin permits gonadotropin secretion; leptin-deficient humans have hypogonadotropic hypogonadism that is corrected by leptin therapy. A non-core neuroendocrine role. Supporting Evidence: PMID:12393845 through its age-dependent effects on gonadotropin secretion, facilitated appropriately timed pubertal development |
| GO:0035360 positive regulation of peroxisome proliferator activated receptor signaling pathway | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of PPAR signaling (rat ortholog). Reason: Leptin acts on this process only indirectly, as an extracellular ligand that activates LEPR-JAK2 signalling in target cells. The annotation is not wrong as a regulatory effect, but it is one of many pleiotropic downstream consequences of receptor activation and does not describe the hormone's own activity. Supporting Evidence: file:human/LEP/LEP-uniprot.txt has central and peripheral effects by binding LEPR |
| GO:0035556 intracellular signal transduction | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Intracellular signal transduction (rat ortholog). Reason: Leptin is an extracellular ligand; the intracellular cascade is executed by LEPR, JAK2 and STATs. The specific pathway term leptin-mediated signaling pathway is already accepted. Supporting Evidence: file:human/LEP/LEP-uniprot.txt has central and peripheral effects by binding LEPR |
| GO:0035630 bone mineralization involved in bone maturation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Bone mineralization involved in bone maturation (rat ortholog). Reason: Leptin influences bone mass largely through central regulation; it does not participate in mineralization. Leptin acts on this process only indirectly, as an extracellular ligand that activates LEPR-JAK2 signalling in target cells. The annotation is not wrong as a regulatory effect, but it is one of many pleiotropic downstream consequences of receptor activation and does not describe the hormone's own activity. Supporting Evidence: file:human/LEP/LEP-uniprot.txt also regulates bone mass and secretion of hypothalamo-pituitary-adrenal hormones |
| GO:0038108 negative regulation of appetite by leptin-mediated signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Negative regulation of appetite by leptin-mediated signaling pathway (IBA). Reason: This is the core physiological process of leptin: leptin acts on hypothalamic LEPR to suppress food intake. Supported by ob/ob rescue and by leptin replacement in congenitally leptin-deficient humans. Supporting Evidence: PMID:7624777 The protein reduced food intake and increased energy expenditure in ob/ob mice. PMID:12393845 with sustained, beneficial effects on appetite, fat mass, hyperinsulinemia, and hyperlipidemia PMID:9202122 The severe obesity found in these congenitally leptin-deficient subjects provides the first genetic evidence that leptin is an important regulator of energy balance in humans. |
| GO:0038108 negative regulation of appetite by leptin-mediated signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: Negative regulation of appetite by leptin-mediated signaling pathway (IEA). Reason: This is the core physiological process of leptin: leptin acts on hypothalamic LEPR to suppress food intake. Supported by ob/ob rescue and by leptin replacement in congenitally leptin-deficient humans. Supporting Evidence: PMID:7624777 The protein reduced food intake and increased energy expenditure in ob/ob mice. PMID:12393845 with sustained, beneficial effects on appetite, fat mass, hyperinsulinemia, and hyperlipidemia PMID:9202122 The severe obesity found in these congenitally leptin-deficient subjects provides the first genetic evidence that leptin is an important regulator of energy balance in humans. |
| GO:0038108 negative regulation of appetite by leptin-mediated signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: Negative regulation of appetite by leptin-mediated signaling pathway (ISS). Reason: This is the core physiological process of leptin: leptin acts on hypothalamic LEPR to suppress food intake. Supported by ob/ob rescue and by leptin replacement in congenitally leptin-deficient humans. Supporting Evidence: PMID:7624777 The protein reduced food intake and increased energy expenditure in ob/ob mice. PMID:12393845 with sustained, beneficial effects on appetite, fat mass, hyperinsulinemia, and hyperlipidemia PMID:9202122 The severe obesity found in these congenitally leptin-deficient subjects provides the first genetic evidence that leptin is an important regulator of energy balance in humans. |
| GO:0042102 positive regulation of T cell proliferation | IDA PMID:25060689 Leptin modulates autophagy in human CD4+CD25- conventional T... | KEEP AS NON CORE | Summary: Positive regulation of T cell proliferation (IDA). Reason: Leptin promotes proliferation of human conventional CD4+ T cells, and leptin-deficient patients have impaired T cell proliferation reversed by therapy. A genuine non-core immune role. Supporting Evidence: PMID:25060689 autophagy and proliferation are controlled by leptin during TCR-engagement PMID:12393845 Leptin deficiency was associated with reduced numbers of circulating CD4(+) T cells and impaired T cell proliferation and cytokine release |
| GO:0042269 regulation of natural killer cell mediated cytotoxicity | IDA PMID:12504075 Expression of leptin receptors and response to leptin stimul... | KEEP AS NON CORE | Summary: Leptin regulates NK cell proliferation and cytotoxicity. Reason: Human NK cell lines express LEPR and respond to leptin with STAT3 activation, proliferation and increased cytotoxicity; a non-core immune effect. Supporting Evidence: PMID:12504075 The IL-2-independent YT cells were dose-dependently responsible for leptin stimulation to manifest rapid proliferation and strong cytotoxicity against tumor targets. |
| GO:0042307 positive regulation of protein import into nucleus | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of protein import into nucleus (mouse ortholog). Reason: Nuclear import of STAT3 is a downstream event of LEPR-JAK2 signalling, not an activity of leptin. Leptin acts on this process only indirectly, as an extracellular ligand that activates LEPR-JAK2 signalling in target cells. The annotation is not wrong as a regulatory effect, but it is one of many pleiotropic downstream consequences of receptor activation and does not describe the hormone's own activity. Supporting Evidence: PMID:17344214 leptin induced Stat3-phosphorylation-dependent proliferation of MCF7 cells |
| GO:0043066 negative regulation of apoptotic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Negative regulation of apoptotic process (rat ortholog). Reason: Leptin acts on this process only indirectly, as an extracellular ligand that activates LEPR-JAK2 signalling in target cells. The annotation is not wrong as a regulatory effect, but it is one of many pleiotropic downstream consequences of receptor activation and does not describe the hormone's own activity. Supporting Evidence: file:human/LEP/LEP-uniprot.txt has central and peripheral effects by binding LEPR |
| GO:0043235 signaling receptor complex | IPI PMID:36959263 Mechanism of receptor assembly via the pleiotropic adipokine... | KEEP AS NON CORE | Summary: Part of signaling receptor complex (IPI, structural study). Reason: Leptin forms 3:3 ligand-receptor assemblies with LEPR; as the bound ligand it is part of the active signalling complex. Correct but the core molecular description is hormone activity / leptin receptor binding. Supporting Evidence: PMID:36959263 Leptin induces type I cytokine receptor assemblies featuring 3:3 stoichiometry |
| GO:0043270 positive regulation of monoatomic ion transport | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of monoatomic ion transport (rat ortholog). Reason: Leptin acts on this process only indirectly, as an extracellular ligand that activates LEPR-JAK2 signalling in target cells. The annotation is not wrong as a regulatory effect, but it is one of many pleiotropic downstream consequences of receptor activation and does not describe the hormone's own activity. Supporting Evidence: file:human/LEP/LEP-uniprot.txt has central and peripheral effects by binding LEPR |
| GO:0043410 positive regulation of MAPK cascade | IDA PMID:24340098 Leptin inhibits glucose intestinal absorption via PKC, p38MA... | KEEP AS NON CORE | Summary: Positive regulation of MAPK cascade (IDA). Reason: Leptin increases ERK and p38 phosphorylation in LEPR-expressing cells; a branch of LEPR signalling, non-core. Supporting Evidence: PMID:24340098 Moreover, leptin increased the phosphorylation of ERK, Akt and p38MAPK. |
| GO:0043410 positive regulation of MAPK cascade | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Positive regulation of MAPK cascade (IEA). Reason: Leptin increases ERK and p38 phosphorylation in LEPR-expressing cells; a branch of LEPR signalling, non-core. Supporting Evidence: PMID:24340098 Moreover, leptin increased the phosphorylation of ERK, Akt and p38MAPK. |
| GO:0043410 positive regulation of MAPK cascade | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of MAPK cascade (ISS). Reason: Leptin increases ERK and p38 phosphorylation in LEPR-expressing cells; a branch of LEPR signalling, non-core. Supporting Evidence: PMID:24340098 Moreover, leptin increased the phosphorylation of ERK, Akt and p38MAPK. |
| GO:0044320 cellular response to leptin stimulus | IDA PMID:17344214 leptin-induced growth stimulation of breast cancer cells inv... | MODIFY | Summary: Cellular response to leptin stimulus (IDA, MCF7 cells). Reason: The experiment shows MCF7 cells responding to leptin. Leptin takes part in that response as the ligand whose LEPR binding starts it (GO process terms mean the gene product participates, from whichever side), so the term is true but broader than what the evidence shows leptin doing. The specific process is GO:0033210 leptin-mediated signaling pathway, which is part_of this term. Proposed replacements: leptin-mediated signaling pathway Supporting Evidence: PMID:17344214 leptin induced Stat3-phosphorylation-dependent proliferation of MCF7 cells |
| GO:0045471 response to ethanol | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog-transferred 'response to ethanol' annotation. Reason: This is an ortholog-transferred (Ensembl Compara) annotation that most plausibly reflects regulation of leptin gene expression or circulating leptin levels by this stimulus in rodents, not a function performed by the leptin protein. Leptin is a secreted hormone whose function is to signal through LEPR. Supporting Evidence: PMID:9054940 Leptin is a serum protein which is secreted by adipocytes and thought to play a role in the regulation of body fat. file:human/LEP/LEP-uniprot.txt Key player in the regulation of energy balance and body weight control. |
| GO:0045765 regulation of angiogenesis | IDA PMID:11460888 Potential role of leptin in angiogenesis: leptin induces end... | KEEP AS NON CORE | Summary: Regulation of angiogenesis (IDA). Reason: Leptin is pro-angiogenic via ObR in endothelial cells; non-core. Supporting Evidence: PMID:11460888 leptin's role as an angiogenesis inducer in the normal organ (rat cornea) |
| GO:0045906 negative regulation of vasoconstriction | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Negative regulation of vasoconstriction (rat ortholog). Reason: Leptin acts on this process only indirectly, as an extracellular ligand that activates LEPR-JAK2 signalling in target cells. The annotation is not wrong as a regulatory effect, but it is one of many pleiotropic downstream consequences of receptor activation and does not describe the hormone's own activity. Supporting Evidence: file:human/LEP/LEP-uniprot.txt has central and peripheral effects by binding LEPR |
| GO:0046325 negative regulation of D-glucose import across plasma membrane | IDA PMID:24340098 Leptin inhibits glucose intestinal absorption via PKC, p38MA... | KEEP AS NON CORE | Summary: Negative regulation of D-glucose import across plasma membrane (IDA, Caco-2). Reason: Luminal leptin reduced glucose absorption by enterocyte-like cells through PKC/MAPK/PI3K; a peripheral non-core effect. Supporting Evidence: PMID:24340098 Leptin caused a significant reduction in glucose absorption. |
| GO:0046427 positive regulation of receptor signaling pathway via JAK-STAT | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Positive regulation of receptor signaling pathway via JAK-STAT (IBA). Reason: As the LEPR ligand, leptin activates JAK2-STAT3 signalling; this is a broader description of the same activity captured by the leptin-mediated signaling pathway term. Supporting Evidence: PMID:17344214 leptin induced Stat3-phosphorylation-dependent proliferation of MCF7 cells PMID:12504075 The IL-2-independent YT cells were dose-dependently responsible for leptin stimulation to manifest rapid proliferation and strong cytotoxicity against tumor targets. |
| GO:0046427 positive regulation of receptor signaling pathway via JAK-STAT | IDA PMID:17344214 leptin-induced growth stimulation of breast cancer cells inv... | KEEP AS NON CORE | Summary: Positive regulation of receptor signaling pathway via JAK-STAT (IDA). Reason: As the LEPR ligand, leptin activates JAK2-STAT3 signalling; this is a broader description of the same activity captured by the leptin-mediated signaling pathway term. Supporting Evidence: PMID:17344214 leptin induced Stat3-phosphorylation-dependent proliferation of MCF7 cells PMID:12504075 The IL-2-independent YT cells were dose-dependently responsible for leptin stimulation to manifest rapid proliferation and strong cytotoxicity against tumor targets. |
| GO:0046427 positive regulation of receptor signaling pathway via JAK-STAT | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Positive regulation of receptor signaling pathway via JAK-STAT (IEA). Reason: As the LEPR ligand, leptin activates JAK2-STAT3 signalling; this is a broader description of the same activity captured by the leptin-mediated signaling pathway term. Supporting Evidence: PMID:17344214 leptin induced Stat3-phosphorylation-dependent proliferation of MCF7 cells PMID:12504075 The IL-2-independent YT cells were dose-dependently responsible for leptin stimulation to manifest rapid proliferation and strong cytotoxicity against tumor targets. |
| GO:0046628 positive regulation of insulin receptor signaling pathway | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of insulin receptor signaling pathway (rat ortholog). Reason: Leptin acts on this process only indirectly, as an extracellular ligand that activates LEPR-JAK2 signalling in target cells. The annotation is not wrong as a regulatory effect, but it is one of many pleiotropic downstream consequences of receptor activation and does not describe the hormone's own activity. Supporting Evidence: file:human/LEP/LEP-uniprot.txt In the periphery, increases basal metabolism, influences reproductive function, regulates pancreatic beta-cell function and insulin secretion |
| GO:0046850 regulation of bone remodeling | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Regulation of bone remodeling (IEA). Reason: Leptin regulates bone mass, in rodents substantially through a hypothalamic relay; a genuine but non-core role. Supporting Evidence: PMID:28270795 However, this adipocyte-derived hormone also directs peripheral processes, including immunity, reproduction, and bone metabolism. file:human/LEP/LEP-uniprot.txt also regulates bone mass and secretion of hypothalamo-pituitary-adrenal hormones |
| GO:0046850 regulation of bone remodeling | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Regulation of bone remodeling (ISS). Reason: Leptin regulates bone mass, in rodents substantially through a hypothalamic relay; a genuine but non-core role. Supporting Evidence: PMID:28270795 However, this adipocyte-derived hormone also directs peripheral processes, including immunity, reproduction, and bone metabolism. file:human/LEP/LEP-uniprot.txt also regulates bone mass and secretion of hypothalamo-pituitary-adrenal hormones |
| GO:0046850 regulation of bone remodeling | NAS PMID:28270795 The Leptin Receptor Complex: Heavier Than Expected? | KEEP AS NON CORE | Summary: Regulation of bone remodeling (NAS). Reason: Leptin regulates bone mass, in rodents substantially through a hypothalamic relay; a genuine but non-core role. Supporting Evidence: PMID:28270795 However, this adipocyte-derived hormone also directs peripheral processes, including immunity, reproduction, and bone metabolism. file:human/LEP/LEP-uniprot.txt also regulates bone mass and secretion of hypothalamo-pituitary-adrenal hormones |
| GO:0046881 positive regulation of follicle-stimulating hormone secretion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of follicle-stimulating hormone secretion (rat ortholog). Reason: Leptin permits gonadotropin secretion; leptin-deficient humans have hypogonadotropic hypogonadism that is corrected by leptin therapy. A non-core neuroendocrine role. Supporting Evidence: PMID:12393845 through its age-dependent effects on gonadotropin secretion, facilitated appropriately timed pubertal development |
| GO:0048639 positive regulation of developmental growth | IDA PMID:17957153 Milk intake and feeding behavior in the first week of life a... | UNDECIDED | Summary: Positive regulation of developmental growth from a cord-blood feeding study. Reason: The cached abstract of PMID:17957153 reports that cord leptin was not related to milk intake or feed frequency and does not describe a growth-promoting role for leptin. Without the full text we cannot verify what the curator used. Supporting Evidence: PMID:17957153 Total cord ghrelin and leptin are not directly related to milk intake or feed frequency in the first week of life. |
| GO:0050892 intestinal absorption | IDA PMID:24340098 Leptin inhibits glucose intestinal absorption via PKC, p38MA... | MARK AS OVER ANNOTATED | Summary: Intestinal absorption (IDA, Caco-2 cells). Reason: Leptin reduces glucose absorption; it regulates rather than performs intestinal absorption, and the more precise regulatory term (negative regulation of D-glucose import across plasma membrane) is retained. Supporting Evidence: PMID:24340098 Leptin caused a significant reduction in glucose absorption. |
| GO:0050901 leukocyte tethering or rolling | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Leukocyte tethering or rolling (rat ortholog). Reason: Leptin acts on this process only indirectly, as an extracellular ligand that activates LEPR-JAK2 signalling in target cells. The annotation is not wrong as a regulatory effect, but it is one of many pleiotropic downstream consequences of receptor activation and does not describe the hormone's own activity. Supporting Evidence: file:human/LEP/LEP-uniprot.txt Increases phagocytosis by macrophages and enhances secretion of pro-inflammatory mediators. |
| GO:0050999 regulation of nitric-oxide synthase activity | IDA PMID:15899045 Signalling pathway involved in nitric oxide synthase type II... | KEEP AS NON CORE | Summary: Regulation of nitric-oxide synthase activity (IDA, chondrocytes). Reason: Leptin synergises with IL-1 to induce NOS type II in chondrocytes; the effect is mainly on NOS2 induction, downstream of LEPR. Non-core. Supporting Evidence: PMID:15899045 This study indicates that leptin plays a proinflammatory role, in synergy with IL-1, by inducing NOS type II |
| GO:0051051 negative regulation of transport | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Negative regulation of transport (ARBA). Reason: Very broad machine-learning-derived term; the specific supported effect (reduced intestinal glucose uptake) is captured separately. Supporting Evidence: PMID:24340098 Leptin caused a significant reduction in glucose absorption. |
| GO:0051428 peptide hormone receptor binding | IEA GO_REF:0000107 | MODIFY | Summary: Peptide hormone receptor binding (rat ortholog). Reason: Leptin binds the leptin receptor, a class I cytokine receptor; the specific term leptin receptor binding is appropriate. Proposed replacements: leptin receptor binding Supporting Evidence: file:human/LEP/LEP-uniprot.txt has central and peripheral effects by binding LEPR PMID:36959263 Leptin induces type I cytokine receptor assemblies featuring 3:3 stoichiometry |
| GO:0051726 regulation of cell cycle | IDA PMID:17344214 leptin-induced growth stimulation of breast cancer cells inv... | KEEP AS NON CORE | Summary: Regulation of cell cycle (IDA). Reason: Leptin promotes S-phase entry and cyclin D1 expression in LEPR-expressing breast cancer cells via STAT3; non-core. Supporting Evidence: PMID:17344214 Leptin increased MCF7 cell population in the S-phase of the cell cycle along with a robust increase in CYCLIN D1 expression. |
| GO:0051726 regulation of cell cycle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Regulation of cell cycle (IEA). Reason: Leptin promotes S-phase entry and cyclin D1 expression in LEPR-expressing breast cancer cells via STAT3; non-core. Supporting Evidence: PMID:17344214 Leptin increased MCF7 cell population in the S-phase of the cell cycle along with a robust increase in CYCLIN D1 expression. |
| GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Positive regulation of PI3K/AKT signal transduction (IEA). Reason: Leptin activates PI3K-AKT downstream of LEPR; a branch of receptor signalling, non-core. Supporting Evidence: PMID:24340098 Moreover, leptin increased the phosphorylation of ERK, Akt and p38MAPK. |
| GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of PI3K/AKT signal transduction (ISS). Reason: Leptin activates PI3K-AKT downstream of LEPR; a branch of receptor signalling, non-core. Supporting Evidence: PMID:24340098 Moreover, leptin increased the phosphorylation of ERK, Akt and p38MAPK. |
| GO:0060587 regulation of lipoprotein lipid oxidation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Regulation of lipoprotein lipid oxidation (rat/mouse ortholog transfer). Reason: Leptin acts on this process only indirectly, as an extracellular ligand that activates LEPR-JAK2 signalling in target cells. The annotation is not wrong as a regulatory effect, but it is one of many pleiotropic downstream consequences of receptor activation and does not describe the hormone's own activity. Supporting Evidence: file:human/LEP/LEP-uniprot.txt has central and peripheral effects by binding LEPR |
| GO:0061037 negative regulation of cartilage development | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Negative regulation of cartilage development (rat/mouse ortholog transfer). Reason: Leptin acts on this process only indirectly, as an extracellular ligand that activates LEPR-JAK2 signalling in target cells. The annotation is not wrong as a regulatory effect, but it is one of many pleiotropic downstream consequences of receptor activation and does not describe the hormone's own activity. Supporting Evidence: file:human/LEP/LEP-uniprot.txt has central and peripheral effects by binding LEPR |
| GO:0070093 negative regulation of glucagon secretion | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Negative regulation of glucagon secretion (rat/mouse ortholog transfer). Reason: Leptin acts on this process only indirectly, as an extracellular ligand that activates LEPR-JAK2 signalling in target cells. The annotation is not wrong as a regulatory effect, but it is one of many pleiotropic downstream consequences of receptor activation and does not describe the hormone's own activity. Supporting Evidence: file:human/LEP/LEP-uniprot.txt has central and peripheral effects by binding LEPR |
| GO:0071298 cellular response to L-ascorbic acid | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog-transferred 'cellular response to L-ascorbic acid' annotation. Reason: This is an ortholog-transferred (Ensembl Compara) annotation that most plausibly reflects regulation of leptin gene expression or circulating leptin levels by this stimulus in rodents, not a function performed by the leptin protein. Leptin is a secreted hormone whose function is to signal through LEPR. Supporting Evidence: PMID:9054940 Leptin is a serum protein which is secreted by adipocytes and thought to play a role in the regulation of body fat. file:human/LEP/LEP-uniprot.txt Key player in the regulation of energy balance and body weight control. |
| GO:0071300 cellular response to retinoic acid | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog-transferred 'cellular response to retinoic acid' annotation. Reason: This is an ortholog-transferred (Ensembl Compara) annotation that most plausibly reflects regulation of leptin gene expression or circulating leptin levels by this stimulus in rodents, not a function performed by the leptin protein. Leptin is a secreted hormone whose function is to signal through LEPR. Supporting Evidence: PMID:9054940 Leptin is a serum protein which is secreted by adipocytes and thought to play a role in the regulation of body fat. file:human/LEP/LEP-uniprot.txt Key player in the regulation of energy balance and body weight control. |
| GO:0090335 regulation of brown fat cell differentiation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Regulation of brown fat cell differentiation (IEA). Reason: Leptin acts on this process only indirectly, as an extracellular ligand that activates LEPR-JAK2 signalling in target cells. The annotation is not wrong as a regulatory effect, but it is one of many pleiotropic downstream consequences of receptor activation and does not describe the hormone's own activity. Supporting Evidence: PMID:27986616 the ob/ob mice have decreased thermogenic markers |
| GO:0090335 regulation of brown fat cell differentiation | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Regulation of brown fat cell differentiation (ISS). Reason: Leptin acts on this process only indirectly, as an extracellular ligand that activates LEPR-JAK2 signalling in target cells. The annotation is not wrong as a regulatory effect, but it is one of many pleiotropic downstream consequences of receptor activation and does not describe the hormone's own activity. Supporting Evidence: PMID:27986616 the ob/ob mice have decreased thermogenic markers |
| GO:0097009 energy homeostasis | IEA GO_REF:0000107 | ACCEPT | Summary: Energy homeostasis (IEA). Reason: Leptin is the afferent adipostatic signal regulating food intake and energy expenditure; congenital leptin deficiency causes severe hyperphagic obesity. Supporting Evidence: PMID:9202122 The severe obesity found in these congenitally leptin-deficient subjects provides the first genetic evidence that leptin is an important regulator of energy balance in humans. PMID:28270795 leptin and the leptin receptor (ObR) regulate the body weight by balancing food intake and energy expenditure |
| GO:0097009 energy homeostasis | ISS GO_REF:0000024 | ACCEPT | Summary: Energy homeostasis (ISS). Reason: Leptin is the afferent adipostatic signal regulating food intake and energy expenditure; congenital leptin deficiency causes severe hyperphagic obesity. Supporting Evidence: PMID:9202122 The severe obesity found in these congenitally leptin-deficient subjects provides the first genetic evidence that leptin is an important regulator of energy balance in humans. PMID:28270795 leptin and the leptin receptor (ObR) regulate the body weight by balancing food intake and energy expenditure |
| GO:0097009 energy homeostasis | NAS PMID:28270795 The Leptin Receptor Complex: Heavier Than Expected? | ACCEPT | Summary: Energy homeostasis (NAS). Reason: Leptin is the afferent adipostatic signal regulating food intake and energy expenditure; congenital leptin deficiency causes severe hyperphagic obesity. Supporting Evidence: PMID:9202122 The severe obesity found in these congenitally leptin-deficient subjects provides the first genetic evidence that leptin is an important regulator of energy balance in humans. PMID:28270795 leptin and the leptin receptor (ObR) regulate the body weight by balancing food intake and energy expenditure |
| GO:0097696 cell surface receptor signaling pathway via STAT | IDA PMID:27037668 Inhibition of Leptin-ObR Interaction Does not Prevent Leptin... | MODIFY | Summary: Cell surface receptor signaling pathway via STAT (IDA). Reason: Correct but generic; leptin initiates the specific leptin-mediated signaling pathway via LEPR-JAK2-STAT3. Proposed replacements: leptin-mediated signaling pathway Supporting Evidence: PMID:27037668 The adipocyte-derived hormone leptin regulates appetite and energy homeostasis through the activation of leptin receptors (ObR) on hypothalamic neurones |
| GO:0098868 bone growth | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Bone growth (IEA). Reason: Leptin influences bone mass mainly through central regulation; it is not a participant in bone growth itself. Leptin acts on this process only indirectly, as an extracellular ligand that activates LEPR-JAK2 signalling in target cells. The annotation is not wrong as a regulatory effect, but it is one of many pleiotropic downstream consequences of receptor activation and does not describe the hormone's own activity. Supporting Evidence: file:human/LEP/LEP-uniprot.txt also regulates bone mass and secretion of hypothalamo-pituitary-adrenal hormones |
| GO:0098868 bone growth | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Bone growth (ISS). Reason: Leptin influences bone mass mainly through central regulation; it is not a participant in bone growth itself. Leptin acts on this process only indirectly, as an extracellular ligand that activates LEPR-JAK2 signalling in target cells. The annotation is not wrong as a regulatory effect, but it is one of many pleiotropic downstream consequences of receptor activation and does not describe the hormone's own activity. Supporting Evidence: file:human/LEP/LEP-uniprot.txt also regulates bone mass and secretion of hypothalamo-pituitary-adrenal hormones |
| GO:0120162 positive regulation of cold-induced thermogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of cold-induced thermogenesis (IEA). Reason: Leptin increases energy expenditure, and leptin-deficient ob/ob mice have reduced brown-fat thermogenic markers. Part of the energy-expenditure arm of energy homeostasis; kept as non-core. Supporting Evidence: PMID:27986616 the ob/ob mice have decreased thermogenic markers PMID:7624777 The protein reduced food intake and increased energy expenditure in ob/ob mice. |
| GO:0120162 positive regulation of cold-induced thermogenesis | ISS PMID:27986616 Thermogenesis, fatty acid synthesis with oxidation, and infl... | KEEP AS NON CORE | Summary: Positive regulation of cold-induced thermogenesis (ISS). Reason: Leptin increases energy expenditure, and leptin-deficient ob/ob mice have reduced brown-fat thermogenic markers. Part of the energy-expenditure arm of energy homeostasis; kept as non-core. Supporting Evidence: PMID:27986616 the ob/ob mice have decreased thermogenic markers PMID:7624777 The protein reduced food intake and increased energy expenditure in ob/ob mice. |
| GO:1900015 regulation of cytokine production involved in inflammatory response | IDA PMID:19688109 Leptin enhances synthesis of proinflammatory mediators in hu... | KEEP AS NON CORE | Summary: Regulation of cytokine production involved in inflammatory response (IDA). Reason: Leptin enhances production of IL-6, IL-8, NO and PGE2 in inflamed cartilage; a pro-inflammatory peripheral effect. Supporting Evidence: PMID:19688109 Leptin alone or in combination with IL-1 enhanced the expression of iNOS and COX-2, and production of NO, PGE(2), IL-6, and IL-8. |
| GO:1900015 regulation of cytokine production involved in inflammatory response | NAS PMID:28270795 The Leptin Receptor Complex: Heavier Than Expected? | KEEP AS NON CORE | Summary: Regulation of cytokine production involved in inflammatory response (NAS). Reason: Leptin enhances production of IL-6, IL-8, NO and PGE2 in inflamed cartilage; a pro-inflammatory peripheral effect. Supporting Evidence: PMID:19688109 Leptin alone or in combination with IL-1 enhanced the expression of iNOS and COX-2, and production of NO, PGE(2), IL-6, and IL-8. PMID:28270795 However, this adipocyte-derived hormone also directs peripheral processes, including immunity, reproduction, and bone metabolism. |
| GO:1900745 positive regulation of p38MAPK cascade | IDA PMID:24340098 Leptin inhibits glucose intestinal absorption via PKC, p38MA... | KEEP AS NON CORE | Summary: Positive regulation of p38MAPK cascade (IDA). Reason: Leptin increased p38MAPK phosphorylation in Caco-2 cells; downstream of LEPR, non-core. Supporting Evidence: PMID:24340098 Moreover, leptin increased the phosphorylation of ERK, Akt and p38MAPK. |
| GO:1904651 positive regulation of fat cell apoptotic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of fat cell apoptotic process (rat/mouse ortholog transfer). Reason: Leptin acts on this process only indirectly, as an extracellular ligand that activates LEPR-JAK2 signalling in target cells. The annotation is not wrong as a regulatory effect, but it is one of many pleiotropic downstream consequences of receptor activation and does not describe the hormone's own activity. Supporting Evidence: file:human/LEP/LEP-uniprot.txt has central and peripheral effects by binding LEPR |
| GO:1990051 activation of protein kinase C activity | IDA PMID:24340098 Leptin inhibits glucose intestinal absorption via PKC, p38MA... | KEEP AS NON CORE | Summary: Activation of protein kinase C activity (IDA). Reason: The authors conclude leptin reduces glucose absorption by activating PKC; leptin acts indirectly via LEPR, so this is a non-core downstream effect. Supporting Evidence: PMID:24340098 These results suggest that leptin reduces glucose absorption by activating PKC. |
| GO:1990460 leptin receptor binding | IBA GO_REF:0000033 | ACCEPT | Summary: Leptin receptor binding (IBA). Reason: Binding to LEPR is the molecular basis of leptin's hormone activity; structural studies show leptin assembles 3:3 LEPR complexes. Supporting Evidence: PMID:36959263 Leptin induces type I cytokine receptor assemblies featuring 3:3 stoichiometry PMID:27037668 The adipocyte-derived hormone leptin regulates appetite and energy homeostasis through the activation of leptin receptors (ObR) on hypothalamic neurones |
| GO:1990460 leptin receptor binding | IPI PMID:27037668 Inhibition of Leptin-ObR Interaction Does not Prevent Leptin... | ACCEPT | Summary: Leptin receptor binding (IPI). Reason: Binding to LEPR is the molecular basis of leptin's hormone activity; structural studies show leptin assembles 3:3 LEPR complexes. Supporting Evidence: PMID:36959263 Leptin induces type I cytokine receptor assemblies featuring 3:3 stoichiometry PMID:27037668 The adipocyte-derived hormone leptin regulates appetite and energy homeostasis through the activation of leptin receptors (ObR) on hypothalamic neurones |
| GO:2000379 positive regulation of reactive oxygen species metabolic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of reactive oxygen species metabolic process (rat/mouse ortholog transfer). Reason: Leptin acts on this process only indirectly, as an extracellular ligand that activates LEPR-JAK2 signalling in target cells. The annotation is not wrong as a regulatory effect, but it is one of many pleiotropic downstream consequences of receptor activation and does not describe the hormone's own activity. Supporting Evidence: file:human/LEP/LEP-uniprot.txt has central and peripheral effects by binding LEPR |
| GO:2000486 negative regulation of glutamine transport | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Negative regulation of glutamine transport (rat/mouse ortholog transfer). Reason: Leptin acts on this process only indirectly, as an extracellular ligand that activates LEPR-JAK2 signalling in target cells. The annotation is not wrong as a regulatory effect, but it is one of many pleiotropic downstream consequences of receptor activation and does not describe the hormone's own activity. Supporting Evidence: file:human/LEP/LEP-uniprot.txt has central and peripheral effects by binding LEPR |
| GO:2000491 positive regulation of hepatic stellate cell activation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of hepatic stellate cell activation (rat/mouse ortholog transfer). Reason: Leptin acts on this process only indirectly, as an extracellular ligand that activates LEPR-JAK2 signalling in target cells. The annotation is not wrong as a regulatory effect, but it is one of many pleiotropic downstream consequences of receptor activation and does not describe the hormone's own activity. Supporting Evidence: file:human/LEP/LEP-uniprot.txt has central and peripheral effects by binding LEPR |
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