Leptin receptor
Leptin receptor also known as LEP-R or OB-R is a protein that in humans is encoded by the LEPR gene.[5][6] LEP-R functions as a receptor for the fat cell-specific hormone leptin. LEP-R has also been designated as CD295 (cluster of differentiation 295).
After co-discovering the Leptin gene with Jeffrey Friedman et al. in 1994, which involved a reverse genetic/positional cloning strategy to clone ob and db, Rudolph Leibel, working with collaborators at Millennium Pharmaceuticals and colleague Streamson Chua, confirmed cloning of the leptin receptor by demonstrating that an apparent leptin receptor cloned from a choroid plexus library using leptin as ligand, mapped to a physical map that included db and fa.[7]
Function
The leptin hormone regulates adipose-tissue mass through hypothalamus effects on hunger and energy use. It acts through the leptin receptor (LEP-R), a single-transmembrane-domain receptor of the cytokine receptor family.[8] In hypothalamic neurons, adequate leptin receptor function and subsequent regulation of energy metabolism and body weight depends on interactions of the receptor with gangliosides in the cell membrane.[9]
Clinical significance
Variations in the leptin receptor have been associated with obesity[10][11] and with increased susceptibility to Entamoeba histolytica infections.[12]
Animals models
The db/db mouse is a model of obesity, diabetes, and dyslipidemia wherein leptin receptor activity is deficient because the mice are homozygous for a point mutation in the gene for the leptin receptor.[13] In db/db mice, induced swimming helped to overcome obesity by upregulating uncoupling proteins.[14]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000116678 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000057722 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Tartaglia LA, Dembski M, Weng X, Deng N, Culpepper J, Devos R, Richards GJ, Campfield LA, Clark FT, Deeds J, Muir C, Sanker S, Moriarty A, Moore KJ, Smutko JS, Mays GG, Wool EA, Monroe CA, Tepper RI (Feb 1996). "Identification and expression cloning of a leptin receptor, OB-R". Cell. 83 (7): 1263–71. doi:10.1016/0092-8674(95)90151-5. PMID 8548812.
- ^ Winick JD, Stoffel M, Friedman JM (Feb 1997). "Identification of microsatellite markers linked to the human leptin receptor gene on chromosome 1". Genomics. 36 (1): 221–2. doi:10.1006/geno.1996.0455. PMID 8812446.
- ^ Leibel RL (Dec 2008). "Molecular physiology of weight regulation in mice and humans". Int J Obes. 32 (S7): S98-108. doi:10.1038/ijo.2008.245. PMC 2682360. PMID 19136999.
- ^ "Entrez Gene: LEPR leptin receptor".
- ^ Nordström V, Willershäuser M, Herzer S, Rozman J, von Bohlen und Halbach O, Meldner S; et al. (March 12, 2013). "Neuronal Expression of Glucosylceramide Synthase in Central Nervous System Regulates Body Weight and Energy Homeostasis". PLoS Biology. 11 (3): e1001506. doi:10.1371/journal.pbio.1001506.
{{cite journal}}: Explicit use of et al. in:|last=(help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Considine RV, Considine EL, Williams CJ, Nyce MR, Zhang P, Opentanova I, Ohannesian JP, Kolaczynski JW, Bauer TL, Moore JH, Caro JF (March 1996). "Mutation screening and identification of a sequence variation in the human ob gene coding region". Biochem. Biophys. Res. Commun. 220 (3): 735–9. doi:10.1006/bbrc.1996.0473. PMID 8607834.
- ^ Masuo K, Straznicky NE, Lambert GW, Katsuya T, Sugimoto K, Rakugi H, Socratous F, Hastings J, Lambert EA, Ogihara T, Esler MD (June 2008). "Leptin-receptor polymorphisms relate to obesity through blunted leptin-mediated sympathetic nerve activation in a Caucasian male population". Hypertens. Res. 31 (6): 1093–100. doi:10.1291/hypres.31.1093. PMID 18716356.
- ^ Duggal P, Guo X, Haque R, Peterson KM, Ricklefs S, Mondal D, Alam F, Noor Z, Verkerke HP, Marie C, Leduc CA, Chua SC, Myers MG, Leibel RL, Houpt E, Gilchrist CA, Sher A, Porcella SF, Petri WA (March 2011). "A mutation in the leptin receptor is associated with Entamoeba histolytica infection in children". J. Clin. Invest. 121 (3): 1191–8. doi:10.1172/JCI45294. PMC 3049405. PMID 21393862.
- ^ Sharma K, McCue P, Dunn SR (June 2003). "Diabetic kidney disease in the db/db mouse". Am. J. Physiol. Renal Physiol. 284 (6): F1138–44. doi:10.1152/ajprenal.00315.2002. PMID 12736165.
- ^ Oh KS, Kim EY, Yoon M, Lee CM (June 2007). "Swim training improves leptin receptor deficiency-induced obesity and lipid disorder by activating uncoupling proteins". Experimental & Molecular Medicine. 39 (3): 385–94. doi:10.1038/emm.2007.43. PMID 17603293.
Further reading
External links
- LEPR+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.