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Role of Leptin Deficiency, Inefficiency, and Leptin Receptors in Obesity

Biochemical Genetics volume 54, pages 565–572 (2016)Cite this article

Abstract

Leptin protein consists of 167 amino acids, which is mainly secreted from the white adipose tissue. This protein acts on the hypothalamic regions of the brain which control eating behavior, thus playing a significant role in maintaining body’s metabolism. Leptin receptors belong to glycoprotein 130 (gp130) family of cytokine receptors and exist in six isoforms (LEPR a–f), and all the isoforms are encoded by LEPR gene; out of these isoforms, the LEPR-b receptor is the ‘longest form,’ and in most of the cases, mutations in this isoform cause severe obesity. Also, mutations in the leptin gene (LEP) or its receptors gene can lead to obesity. Some biochemical pathways affect the bioactivity of leptin and/or its receptors. To date, eleven pathogenic mutations have been reported in the LEP which are p.L72S, p.N103K, p.R105W, p.H118L, p.S141C, p.W121X c.104_106delTCA, c.135del3bp, c.398delG, c.481_482delCT, and c.163C>T. Different mutations in the LEPR have also been reported as c.2396-1 G>T, c.1675 G>A, p.P316T, etc. In some studies, where leptin was deficient, leptin replacement therapy has shown positive impact by preventing weight gain and obesity.

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Authors and Affiliations

  1. Diabetes and Cardio-Metabolic Disorders Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE), Faisalabad, Pakistan

    Muhammad Wasim, Fazli Rabbi Awan, Syeda Sadia Najam & Haq Nawaz Khan

  2. Obesity and Diabetes Research Laboratory, Department of Chemistry, University of Azad Jammu and Kashmir, Muzaffarabad, Pakistan

    Abdul Rehman Khan

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  1. Muhammad Wasim
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Wasim, M., Awan, F.R., Najam, S.S. et al. Role of Leptin Deficiency, Inefficiency, and Leptin Receptors in Obesity. Biochem Genet 54, 565–572 (2016). https://doi.org/10.1007/s10528-016-9751-z

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Keywords

  • Congenital leptin deficiency
  • LEP
  • LEPR
  • Homozygous mutation
  • Ob
  • Leptin replacement therapy (LRT)
  • Obesity