The leptin receptor , also known as LEP-R or OB-R , is a protein that is encoded in humans by the LEPR gene [1] [2] . LEP-R is a receptor for the hormone leptin , produced primarily by adipose tissue cells. The leptin receptor is also called CD295 ( differentiation cluster 295).
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Rudolph Leibel discovered the leptin gene with Jeffrey Friedman and others in 1994. After a while, while working with employees at Millennium Pharmaceuticals and colleague Streamson Chua, he confirmed the cloning of the leptin receptor using a strategy for cloning ob and db, demonstrating on a physical map that includes db and fa that the leptin receptor was cloned from a network of blood vessels and cells in the ventricles of the brain, used leptin as a ligand [3] . Lepob / ob - lines of mice with the leptin gene mutated on the 6th chromosome. The mutation is autosomal recessive. With this type of mutation, mice develop obesity , hyperinsulinemia, and hypoglycemia . LepRdb / db is a line of mice with a mutation in the leptin receptor gene on the fourth chromosome ; it has an autosomal recessive character. This line is almost identical to the Lepob / ob line. The fa / fa line has a mutation of the leptin receptor gene on the fifth chromosome . This mutation leads to problems with the binding of leptin to the surface of receptor-expressing cells , to the development of resistance to leptin in the brain. With this mutation, mice also develop hyperglycemia , insulin resistance, hyperinsulinemia , hyperlipidemia, and moderate hypertension . In addition, in animals, kidney damage and hypertrophy of the islets of Langerhans are recorded. [four]
Content
Functions
The hormone leptin regulates the mass of adipose tissue by acting on the hypothalamus and affecting appetite and energy expenditure. Normally, leptin suppresses appetite and helps to reduce body weight. Leptin also affects the process of puberty . It acts through the leptin receptor, a single transmembrane receptor from the cytokine family .
Variations
Three types of leptin receptor have been identified:
- hydrophobic leptin receptor
- a leptin membrane receptor having a short intracellular domain and incapable of transducing a hormonal signal,
- a membrane receptor capable of transmitting a hormonal signal and having a long intracellular domain . This type of receptor is most actively expressed in the hypothalamus. It is noteworthy that it has sequences that determine the interaction of the intracellular domain with Janus kinase and transcription proteins, and activates proteins STAT-3, STAT-5, STAT-6 by phosphorylation [5]
Clinical Importance
Modifications in the leptin receptor entail obesity [6] [7] , increased susceptibility to infection with dysentery amoeba [8] and impaired puberty.
Animal Models
mouse db / db are obesity , diabetes, and dyslipidemia models. They have decreased leptin receptor activity, because these mice are homozygous for the point mutation leptin receptor gene [9] . In overcoming db / db obesity, mice were helped by forced swimming due to increased expression of uncoupling proteins [10] .
Notes
- ↑ 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 Identification and expression cloning of a leptin receptor, OB-R (Eng.) // Cell : journal. - Cell Press 1996 .-- February ( vol. 83 , no. 7 ). - P. 1263-1271 . - DOI : 10.1016 / 0092-8674 (95) 90151-5 . - PMID 8548812 .
- ↑ Winick JD, Stoffel M., Friedman JM Identification of microsatellite markers linked to the human leptin receptor gene on chromosome 1 (Eng.) // Genomics : journal. - Academic Press , 1997 .-- February ( vol. 36 , no. 1 ). - P. 221-222 . - DOI : 10.1006 / geno.1996.0455 . - PMID 8812446 .
- ↑ Leibel RL Molecular physiology of weight regulation in mice and humans (Eng.) // Int J Obes : journal. - 2008 .-- December ( vol. 32 , no. S7 ). - P. S98-108 . - DOI : 10.1038 / ijo.2008.245 . - PMID 19136999 .
- ↑ Leshchenko D.V.1, Kostyuk N.V. 1, Belyakova M.B.1, Egorova E.N.1, Minyaev M.V.1 "LEPTIN-DEFICIENT AND LEPTIN-RESISTANT LINES OF RODENTS AS MODELS OF METABOLIC SYNDROME": journal "Modern problems of science and education ”- 2015. - No. 4. - C.2-4.
- ↑ Human Leptin Receptor
- ↑ Considine RV, Considine EL, Williams CJ, Nyce MR, Zhang P., Opentanova I., Ohannesian JP, Kolaczynski JW, Bauer TL, Moore JH, Caro JF Mutation screening and identification of a sequence variation in the human ob gene coding region (English) // Biochem. Biophys. Res. Commun. : journal. - 1996 .-- March ( vol. 220 , no. 3 ). - P. 735-739 . - 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 Leptin-receptor polymorphisms relate to obesity through blunted leptin -mediated sympathetic nerve activation in a Caucasian male population (Eng.) // Hypertens. Res. : journal. - 2008 .-- June ( vol. 31 , no. 6 ). - P. 1093-1100 . - 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 A mutation in the leptin receptor is associated with Entamoeba histolytica infection in children (Eng.) // J. Clin. Invest. : journal. - 2011 .-- March ( vol. 121 , no. 3 ). - P. 1191-1198 . - DOI : 10.1172 / JCI45294 . - PMID 21393862 .
- ↑ Sharma K., McCue P., Dunn SR Diabetic kidney disease in the db / db mouse (Eng.) // American Physiological Society : journal. - 2003 .-- June ( vol. 284 , no. 6 ). - P. F1138-44 . - DOI : 10.1152 / ajprenal.00315.2002 . - PMID 12736165 .
- ↑ Oh KS, Kim EY, Yoon M., Lee CM Swim training improves leptin receptor deficiency-induced obesity and lipid disorder by activating uncoupling proteins (Eng.) // Experimental & Molecular Medicine : journal. - 2007 .-- June ( vol. 39 , no. 3 ). - P. 385-394 . - DOI : 10.1038 / emm.2007.43 . - PMID 17603293 .