Early-onset obesity: monogenic obesity

Abstract

In childhood obesity, multifactorial etiology is the most frequent, result of environmental factors interaction in individuals with a polygenic genetic predisposition and in 5-7% obesity is due to a specific gene mutation or obesity rare syndromes. It is necessary to recognize the different types of “childhood obesity”, a set of various pathologies, diverse etiology, that share the obesity presence from an early age in life and that will require different diagnostic and therapeutic strategies.

Last years we have helped multiple research lines development that have allowed us to deepen the regulatory mechanisms knowledge of energy balance; of the genetic bases on which pathological accumulation of adipose tissue occurs, or does not occur, as well as its function or endocrinological dysfunction analysis The increase number of obesity case studies caused by genetic alterations (syndromic or not), endocrinological or secondary to other underlying conditions has contributed to elucidation the pathophysiological bases of appetite control, satiety and energy expenditure. The discovery advances of patients with monogenic etiology obesity expands the modern pathophysiological bases of obesity. The monogenic obesity etiology preferentially affects the genes involved in the appetite-satiety regulation in the leptin-melanocortin pathway: leptin (LEP), leptin receptor (LEPR), proopiomelanocortin (POMC), pro-protein convertase. subtilisin-kexin type 1 (PCSK1), melanocortin receptor 4 (MC4R), Src-homology-2B adapter protein 1 (SH2B1), steroid receptor coactivator 1 (SRC1), carboxypeptidase E (CPE) and stimulatory polypeptide 1 of the alpha activity of the G protein (GNAS), among the most relevant. Along with them, it is of interest to mention some syndromic entities, such as Bardet-Biedl and Alström syndromes. Consequently, it is necessary to individualize the diagnostic strategy and therapeutic approach to both obesity and its associated comorbidities in each patient. Molecular study helps detect those patients who can benefit from specif.