[Genetic variations in energy balance regulation].

Single nucleotide polymorphism (SNP) near certain genes revealed association of FAT(fat mass and obesity-associated gene), MC4R (melanocortin 4 receptor gene), and other genes with obesity. Participation of the FAT expression products in the regulation of energy balance remains to be clarified. The function of MC4R encoding melanocortin 4 receptor (MC4R) is somewhat better understood. alpha-, beta-, and gamma-MSH encoded by the POMC gene bind to MC4R, reduce food intake, and slow down fat accumulation. Expression of POMC that codes MSH is enhanced by leptin binding to the receptor (LepRb) in hypothalamic neurons. Mutations in human and animal MC4R, POMC, and LEP genes are known to be associated with obesity. More than 60 mutations in MC4R, more than 20 mutations in POMC and fewer LEP mutations have been reported. Nonsense mutations and reading frame shifts block gene expression and thereby disrupt protein synthesis. Missense mutations frequently affect protein folding in endoplasmic reticulum; unfolded or misfolded proteins remain in the cytoplasm and undergo degradation. Certain missence mutations do not interfere with gene expression and folding of proteins but impair their functioning at the periphery. P.S127L mutation in MC4R, p.E206X and p.F144L mutations in POMC as well as other mutations in homozygous and heterozygous forms account for disturbed energy balance in man. The LEP gene has been reported to contain G133fsX15, p.R105X, p.R1O5W, and p.S141C mutations. As a rule, they are associated with obesity and other pathological conditions only in homozygous forms.