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The increasing prevalence of overweight and obesity represents an important challenge, worldwide, for the various health systems. The obesity pandemic is associated with the rapid economic growth which has led to relevant lifestyle changes most of them favoring a chronically positive energy balance. On a global scale, between 1980 and 2013, the cumulative prevalence of overweight and obesity in adults has increased from 29% to 37%. This increase concerns also early youth and childhood: the prevalence of overweight and obesity has reached 23% in developed countries and 13% in developing countries. In Italy, a national surveillance program established in 2007 and financed by the Ministry of Health / CCM (Center for Disease Control and Prevention), provides the updated epidemiological framework for the analysis of the prevalence of weight excess and risky behaviors in primary school children. At the time of the last assessment, overweight children, were 20.9%, while obese children were 9.8%. The obesity pandemic is a maladaptive response to an environment enriched in energy availability and which is not exposed anymore to famine episodes. Individual susceptibility to obesity largely depends on the genetic background on which the environment exerts variable pressure. Obesity, in more than 95% of cases, has a multifactorial pathogenesis and can be considered the prototype of what is generally called "a complex phenotype". In facts, unlike diseases with Mendelian transmission, in which there is substantially a direct correlation between genotype and phenotype, obesity represents the result of an interaction between multiple genetic traits, environmental factor and socio-cultural habits. According to the "thrifty genotype" hypothesis, our genetic heritage has evolved in conditions of reduced food availability, selecting "thrifty genes" favoring the deposition of adipose tissue. In recent decades, the wide availability of high energy food has increased rapidly and the "thrifty" genotype has become a promoter for the development of obesity. Although many gene variants that can favor weight accumulation have been identified, a relevant portion of the genetic makeup underlying obesity remains unexplained until today. Beside allelic variants, quite common in the general population, probably exerting small effects on the risk of obesity, an additional contribution may derive from epigenetic modifications developed by living in an obesogenic environment.