Leptin receptor
| View/Edit Human | View/Edit Mouse |
Leptin receptor also known as LEP-R or OB-R is a protein that in humans is encoded by the LEPR gene.[4][5] 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.[6]
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.[7] 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.[8]
Clinical significance
Variations in the leptin receptor have been associated with obesity[9][10] and with increased susceptibility to Entamoeba histolytica infections.[11]
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.[12] In db/db mice, induced swimming helped to overcome obesity by upregulating uncoupling proteins.[13]
References
- ↑ "Diseases that are genetically associated with OB-R view/edit references on wikidata".
- ↑ "Human PubMed Reference:".
- ↑ "Mouse PubMed Reference:".
- ↑ 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.
- ↑ 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
- Heshka JT, Jones PJ (2001). "A role for dietary fat in leptin receptor, OB-Rb, function.". Life Sci. 69 (9): 987–1003. doi:10.1016/S0024-3205(01)01201-2. PMID 11508653.
- Chen H, Charlat O, Tartaglia LA, et al. (1996). "Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice". Cell. 84 (3): 491–5. doi:10.1016/S0092-8674(00)81294-5. PMID 8608603.
- Cioffi JA, Shafer AW, Zupancic TJ, et al. (1996). "Novel B219/OB receptor isoforms: possible role of leptin in hematopoiesis and reproduction". Nat. Med. 2 (5): 585–9. doi:10.1038/nm0596-585. PMID 8616721.
- Considine RV, Considine EL, Williams CJ, et al. (1996). "The hypothalamic leptin receptor in humans: identification of incidental sequence polymorphisms and absence of the db/db mouse and fa/fa rat mutations". Diabetes. 45 (7): 992–4. doi:10.2337/diabetes.45.7.992. PMID 8666155.
- Chung WK, Power-Kehoe L, Chua M, Leibel RL (1996). "Mapping of the OB receptor to 1p in a region of nonconserved gene order from mouse and rat to human". Genome Res. 6 (5): 431–8. doi:10.1101/gr.6.5.431. PMID 8743992.
- Bennett BD, Solar GP, Yuan JQ, et al. (1997). "A role for leptin and its cognate receptor in hematopoiesis". Curr. Biol. 6 (9): 1170–80. doi:10.1016/S0960-9822(02)70684-2. PMID 8805376.
- Luoh SM, Di Marco F, Levin N, et al. (1997). "Cloning and characterization of a human leptin receptor using a biologically active leptin immunoadhesin". J. Mol. Endocrinol. 18 (1): 77–85. doi:10.1677/jme.0.0180077. PMID 9061609.
- Echwald SM, Sørensen TD, Sørensen TI, et al. (1997). "Amino acid variants in the human leptin receptor: lack of association to juvenile onset obesity". Biochem. Biophys. Res. Commun. 233 (1): 248–52. doi:10.1006/bbrc.1997.6430. PMID 9144432.
- Thompson DB, Ravussin E, Bennett PH, Bogardus C (1997). "Structure and sequence variation at the human leptin receptor gene in lean and obese Pima Indians". Hum. Mol. Genet. 6 (5): 675–9. doi:10.1093/hmg/6.5.675. PMID 9158141.
- Gotoda T, Manning BS, Goldstone AP, et al. (1997). "Leptin receptor gene variation and obesity: lack of association in a white British male population". Hum. Mol. Genet. 6 (6): 869–76. doi:10.1093/hmg/6.6.869. PMID 9175732.
- Bailleul B, Akerblom I, Strosberg AD (1997). "The leptin receptor promoter controls expression of a second distinct protein". Nucleic Acids Res. 25 (14): 2752–8. doi:10.1093/nar/25.14.2752. PMC 146799. PMID 9207021.
- Chung WK, Power-Kehoe L, Chua M, et al. (1997). "Exonic and intronic sequence variation in the human leptin receptor gene (LEPR)". Diabetes. 46 (9): 1509–11. doi:10.2337/diab.46.9.1509. PMID 9287054.
- Bjørbaek C, Uotani S, da Silva B, Flier JS (1998). "Divergent signaling capacities of the long and short isoforms of the leptin receptor". J. Biol. Chem. 272 (51): 32686–95. doi:10.1074/jbc.272.51.32686. PMID 9405487.
- Clément K, Vaisse C, Lahlou N, et al. (1998). "A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction". Nature. 392 (6674): 398–401. doi:10.1038/32911. PMID 9537324.
- Carpenter LR, Farruggella TJ, Symes A, et al. (1998). "Enhancing leptin response by preventing SH2-containing phosphatase 2 interaction with Ob receptor". Proc. Natl. Acad. Sci. U.S.A. 95 (11): 6061–6. doi:10.1073/pnas.95.11.6061. PMC 27585. PMID 9600917.
- Kielar D, Clark JS, Ciechanowicz A, et al. (1998). "Leptin receptor isoforms expressed in human adipose tissue". Metab. Clin. Exp. 47 (7): 844–7. doi:10.1016/S0026-0495(98)90124-X. PMID 9667233.
- Haniu M, Arakawa T, Bures EJ, et al. (1998). "Human leptin receptor. Determination of disulfide structure and N-glycosylation sites of the extracellular domain". J. Biol. Chem. 273 (44): 28691–9. doi:10.1074/jbc.273.44.28691. PMID 9786864.
- Haft CR, de la Luz Sierra M, Barr VA, et al. (1998). "Identification of a Family of Sorting Nexin Molecules and Characterization of Their Association with Receptors". Mol. Cell. Biol. 18 (12): 7278–87. doi:10.1128/mcb.18.12.7278. PMC 109309. PMID 9819414.
External links
- LEPR protein, human at the US 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.
This article is issued from Wikipedia - version of the 8/12/2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.