Melanocortin 4 receptor mutation in obesity  

作　　者：Gumpeny R Sridhar Lakshmi Gumpeny 

机构地区：[1]Department of Endocrinology and Diabetes,Endocrine and Diabetes Centre,Visakhapatnam 530002,Andhra Pradesh,India [2]Department of Internal Medicine,Gayatri Vidya Parishad Institute of Healthcare and Medical Technology,Visakhapatnam 530048,Andhra Pradesh,India

出　　处：《World Journal of Experimental Medicine》2024年第4期120-128,共9页世界实验医学杂志（英文）

摘　　要：Obesity is increasingly prevalent worldwide,with genetic factors contributing to its development.The hypothalamic leptin-melanocortin pathway is central to the regulation of appetite and weight;leptin activates the proopiomelanocortin neurons,leading to the production of melanocortin peptides;these in turn act on melanocortin 4 receptors(MC4R)which suppress appetite and increase energy expenditure.MC4R mutations are responsible for syndromic and non-syndromic obesity.These mutations are classified based on their impact on the receptor's life cycle:i.e.null mutations,intracellular retention,binding defects,signaling defects,and variants of unknown function.Clinical manifestations of MC4R mutations include early-onset obesity,hyperphagia,and metabolic abnormalities such as hyperinsulinemia and dyslipidemia.Management strategies for obesity due to MC4R mutations have evolved with the development of targeted therapies such as Setmelanotide,an MC4R agonist which can reduce weight and manage symptoms without adverse cardiovascular effects.Future research directions must include expansion of population studies to better understand the epidemiology of MC4R mutations,exploration of the molecular mechanisms underlying MC4R signaling,and development of new therapeutic agents.Understanding the interaction between MC4R and other genetic and environmental factors will be key to advancing both the prevention and treatment of obesity.

关 键 词：Leptin-melanocortin pathway DOWNSTREAM G protein Cyclic AMP MUTATION Obesity syndromes Screening Setmelanotide 

分 类 号：R589[医药卫生—内分泌]