Melanocortin-4-Receptor Autoantibodies: A New Player in Obesity

Extract

The rise in human obesity, which has been observed worldwide, has attracted the attention of both basic scientists and physicians alike. The fundamental basis of obesity is the imbalance between an individual’s food intake and the energy expenditure. Energy homeostasis is a carefully orchestrated event in humans and animals, involving both peripheral organs like liver, adipose tissue, pancreas, and stomach as well as the central nervous system (1). The communication between the peripheral organs and the central nervous system is achieved via various signaling molecules secreted by these organs such as leptin, insulin, glucose, and various satiety signals. The central integrating circuits for food intake are located in the hypothalamus (2). Well accepted is the thesis that, carrying excess adipose tissue (fat) results in insulin-resistant diabetes mellitus, hypertriglyceridemia, hepatic steatosis, and cardiovascular diseases.

From the standpoint of etiopathology, obesity can be broadly divided into two basic varieties. The more common variant involves multiple molecular components, presumably arising from multiple genetic defects (polygenic obesity) and the interaction of these genetic variations with the environment, leading to the accumulation of excess adipose tissue (3, 4). Less common are the rare monogenic forms of obesity such as those attributed to defects in genes like leptin, leptin receptor, carboxypeptidase E, tubby, or those involved in energy homeostasis and satiety regulation in the hypothalamus, such as proopiomelanocortin (POMC), cocaine and amphetamine-related transcript (CART), the melanocortin system, such as melanocortin 4 receptor (MC4R), single-minded homolog 1 (Drosophila) (SIM1), brain-derived neurotrophic factor (BDNF), and its associated neutrotrophic tyrosine kinase receptor (TRKB/NTRK2) (3, 5).