Wasim Muhammad, Awan Fazli Rabbi, Najam Syeda Sadia, Khan Abdul Rehman, Khan Haq Nawaz
Diabetes and Cardio-Metabolic Disorders Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE), Faisalabad, Pakistan.
Obesity and Diabetes Research Laboratory, Department of Chemistry, University of Azad Jammu and Kashmir, Muzaffarabad, Pakistan.
Biochem Genet. 2016 Oct;54(5):565-72. doi: 10.1007/s10528-016-9751-z. Epub 2016 Jun 16.
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.
瘦素蛋白由167个氨基酸组成，主要由白色脂肪组织分泌。这种蛋白质作用于大脑中控制饮食行为的下丘脑区域，从而在维持身体新陈代谢方面发挥重要作用。瘦素受体属于细胞因子受体的糖蛋白130（gp130）家族，存在六种异构体（LEPR a - f），所有这些异构体均由LEPR基因编码；在这些异构体中，LEPR - b受体是“最长形式”，在大多数情况下，该异构体的突变会导致严重肥胖。此外，瘦素基因（LEP）或其受体基因的突变也可导致肥胖。一些生化途径会影响瘦素和/或其受体的生物活性。迄今为止，已在LEP中报道了11种致病突变，分别是p.L72S、p.N103K、p.R105W、p.H118L、p.S141C、p.W121X、c.104_106delTCA、c.135del3bp、c.398delG、c.481_482delCT和c.163C>T。在LEPR中也报道了不同的突变，如c.2396 - 1 G>T、c.1675 G>A、p.P316T等。在一些研究中，当瘦素缺乏时，瘦素替代疗法通过防止体重增加和肥胖显示出积极影响。
