OBESITÀ: PANDEMIA DEL XXI SECOLO. TRA AMBIENTE E GENETICA

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.

Genetic explanations 1: the thrifty genotype and its variants

The thrifty genotype proposes that populations susceptible to CVD and DM2 have been subjected to intermittent, serious food shortages and have evolved to cope, e.g. through insulin resistance. This means their glucose is not readily entering the muscle to be used there but is preferentially used by the brain and liver. Glucose is converted to fat in the liver and stored for times of food scarcity. This thrifty state is not, however, beneficial in modern times where food is plentiful. This hypothesis remains a common explanation, including for South Asians’ susceptibility to DM2. The hypothesis has lost support, mostly because of lack of confirmatory empirical data, but has sparked-off new ideas, e.g. the mitochondrial efficiency hypothesis as an adaptation to climatic change, and the predation release hypothesis which sees diminishing need for leanness and agility as triggering higher obesity prevalence. These newer ideas need more research.

An Evolutionary Perspective of Nutrition and Inflammation as Mechanisms of Cardiovascular Disease

When cardiovascular diseases are viewed from an evolutionary biology perspective, a heightened thrifty and an inflammatory design could be their mechanisms. Human ancestors confronted a greater infectious load and were subjected to the selection for proinflammatory genes and a strong inflammatory function. Ancestors also faced starvation periods that pressed for a thrifty genotype which caused fat accumulation. The pressure of sustaining gluconeogenesis during periods of poor nourishment selected individuals with insulin resistance. Obesity induces a proinflammatory state due to the secretion of adipokines which underlie cardiometabolic diseases. Our actual lifestyle needs no more of such proinflammatory and thrifty genotypes and these ancestral genes might increase predisposition to diseases. Risk factors for atherosclerosis and diabetes are based on inflammatory and genetic foundations that can be accounted for by excess fat. Longevity has also increased in recent times and is related to a proinflammatory response with cardiovascular consequences. If human ancestral lifestyle could be recovered by increasing exercise and adapting a calorie restriction diet, obesity would decrease and the effects on chronic low-grade inflammation would be limited. Thereby, the rates of both atherosclerosis and diabetes could be reduced.