LEP (leptin) curation notes

Deep research: LEP-deep-research-falcon.md (Falcon, second attempt; the first timed out) completed after
the review was drafted and is consistent with it; the review was written from cached publications and UniProt, with
literature located through PubMed.

Core biology

• Leptin is a secreted four-helix-bundle cytokine-like hormone made mainly by adipocytes
  PMID:7984236.
• It circulates in plasma and acts as an endocrine signal of fat stores; recombinant protein
  reduces food intake and raises energy expenditure in ob/ob mice
  PMID:7624777.
• Receptor: LEPR (OB-R), a class I cytokine receptor
  PMID:8548812.
  Leptin assembles 3:3 LEPR complexes
  PMID:36959263.
• Human genetics: homozygous LEP frameshift causes severe early-onset obesity
  PMID:9202122.
• Leptin replacement corrects appetite, puberty (via gonadotropins), thyroid axis and T cell defects
  PMID:12393845.

Curation approach

• Core: hormone activity / leptin receptor binding (MF); leptin-mediated signaling pathway,
  negative regulation of appetite by leptin-mediated signaling pathway, energy homeostasis (BP);
  extracellular region (CC).
• Reproductive, immune, angiogenic, bone and other peripheral effects are kept as non-core:
  they are real consequences of LEPR activation in target cells.
• Ortholog-transferred "response to X" terms mostly describe regulation of LEP expression
  (leptin levels respond to nutrition, insulin, hormones), not leptin function; marked over-annotated.
• Cytosol and DNA binding contradict a signal-peptide secreted hormone; removed.
• "cellular response to leptin stimulus" (IDA, MCF7) describes the responding cells, not the
  ligand; modified to leptin-mediated signaling pathway.
• Two IDA annotations from PMID:17957153 (placenta development; positive regulation of
  developmental growth) cannot be reconciled with the cached abstract (cord leptin unrelated to
  neonatal feeding); left UNDECIDED rather than removed, since the full text is not cached.
• GO:0005615 extracellular space is obsolete in the current GO release; core location uses
  GO:0005576 extracellular region.