"more than 4000 interactions were identified from high-throughput, yeast two-hybrid (HT=Y2H) screens"

"Our screen revealed that deletion of nhr-49 significantly altered the expression of 13 genes, including six genes predicted to be involved in fatty acid β-oxidation, three genes involved in fatty acid desaturation"

"nhr-49(nr2041) worms lived only 6–8 d as adults, significantly shorter than the 15 to 18-d life span of N2 wild-type (WT) animals"

"the effect of fat-7 RNAi on life span was even more potent than nhr-49 deletion, reducing adult life span to 3–5 d"

"we report the identification of MDT-15, a subunit of the C. elegans Mediator complex, as an NHR-49-interacting protein and transcriptional coactivator"

"mdt-15 RNAi affected additional FA-metabolism genes (including the third FA-Δ9-desaturase, fat-6) that are regulated independently of NHR-49"

"We found an RNAi clone, nhr-80, that caused C. elegans to accumulate increased levels of 18:0"

"These data indicate a 10% decrease in mean lifespan between wild type and nhr-80 mutants, the difference between wild type and nhr-49 mutants is much greater with a 41% reduction in mean lifespan"

"NHR-80 is required for increasing fat-7 expression in situations where higher fat-7 levels are necessary"

"we present an expanded C. elegans protein-protein interaction network"

"we have analyzed the expression of about 227 GFP-tagged proteins that show localized expression in the body wall muscle of this nematode"

"We show that NHR-49 regulates distinct subsets of its target genes by partnering with at least two other distinct nuclear receptors"

"Gene expression profiles suggest that NHR-49 partners with NHR-66 to regulate sphingolipid and lipid remodeling genes and with NHR-80 to regulate genes involved in fatty acid desaturation"

"nhr-49 animals had significantly altered mitochondrial morphology"

"we comprehensively characterize such network rewiring for C. elegans transcription factors (TFs) within and across four newly delineated molecular networks"

"Seven of these transcription factors--AHA-1, CEH-18, HIF-1, JUN-1, NHR-27, NHR-49 and the CREB homolog-1 (CRH-1)-interacting protein TAF-4--were also essential for isp-1 life extension."

"NHR-49 acts in intestine to inhibit lipids accumulation via activation of IPLA-2"

"EGL-4 acts in sensory neurons to enhance lysosomal lipid accumulation through inhibiting the DAF-3/SMAD pathway, whereas NHR-49 acts in intestine"

"nhr-49 has variable degrees of relevance for different physiological alterations that influence aging. It is critical for the longevity mediated by reproductive signals but is not central to the lifespan changes resulting from reduced IIS"

"NHR-49 is transcriptionally up-regulated by DAF-16 and TCER-1 in the soma upon germline removal"

"In adults, it was visible in all somatic tissues (Fig"

"NHR-49 causes the increased expression of multiple genes involved in fatty-acid β-oxidation and desaturation"

"Nuclear hormone receptors nhr-49 and nhr-80, previously demonstrated to physically interact (10), were both required for lipl-4–and lbp-8–mediated longevity"

"no binding was detected between NHR-49 and OEA or OEA analogue"

"acs-2 transcription was increased more than 15-fold in lipl-4 Tg animals; this effect was dependent on nhr-49 and nhr-80"

"nhr-49 and nhr-80 functioned solely as executors"

"lipid accumulation was abrogated in F1 or F2 descendants of these mutants"

"daf-16, sbp-1, nhr-49 and nhr-80 function in parallel pathway during the stress of lipid accumulation in F1 generation"

"nhr-49 is not only required to induce fmo-2, but controls a broad transcriptional response to hypoxia"

"only 25% of nhr-49 and hif-1 null mutant animals reached at least the L4 stage by that time"

"Expression is seen in the head, intestine, and hypodermal seam cells"

"**NHR-49 is a sequence-specific transcription factor of the nuclear receptor superfamily**. It is widely described as functionally comparable to mammalian lipid-sensing nuclear receptors, especially **PPARα** (functional analogy) and **HNF4α** (structural similarity), and is among the best-characterized *C. elegans* NHRs"

"the central mechanistic theme is that **NHR-49 coordinates transcriptional programs that balance lipid catabolism (β-oxidation), fatty-acid desaturation, lipid remodeling, and stress-protective responses**"

"**Primary function**: NHR-49 acts as a **transcriptional regulator** that can both **activate** and **repress** metabolic gene programs. - It activates gene modules involved in **fatty-acid β-oxidation** (including canonical targets such as **acs-2, cpt-5, ech-1**) and regulates **fatty-acid desaturation** genes (**fat-5, fat-6, fat-7**)"

"NHR-49 was shown to regulate distinct gene subsets via **partnerships with other NHRs**, notably: - **NHR-80**: linked to regulation of **fatty-acid desaturase** genes. - **NHR-66**: linked to regulation of **sphingolipid/lipid remodeling** genes."

"Multiple studies converge on **MDT-15 (Mediator subunit)** as a critical co-regulator for NHR-49-driven transcriptional outputs in metabolism and stress programs"

"Evidence strongly supports that **the LBD is functionally important** and likely ligand-responsive, but **a definitive endogenous ligand for NHR-49 is not established**."

"A major mechanistic expansion beyond “lipid metabolism” is an **essential hypoxia survival pathway** controlled by NHR-49 that operates **in parallel to HIF-1**, with NHR-49 being required for hypoxia-induced autophagosome formation (LGG-1::GFP foci) in seam cells"

"A 2024 Genes & Development study places NHR-49/MDT-15 as a signaling module that links lipid metabolic remodeling to **HSF-1-dependent heat shock response** and proteostasis"

"A 2024 Cells paper identifies a **cell-autonomous neuronal role**: loss of nhr-49 causes impaired pathogen lawn avoidance (PA14) associated with **prolonged URX calcium transients after O2 upshift**, and neuronal rescue in URX/AQR/PQR improves both behavior and calcium kinetics"

"Loss of **nhr-49** causes high fat, impaired fasting response, shortened lifespan, altered mitochondrial morphology and function, defective pathogen avoidance, and increased sensitivity to oxidative stress, hypoxia, and infection"

"NHR-49 is required for induction of detoxification programs (phase II enzymes) in oxidative stress contexts and works with MDT-15"