Narrative Review of Human Adiposity: From Evolutionary Energy-Thriftiness and Ancestral Wellness to the Modern Inflammatory-Related Illness. The Role of Lifestyle Transition

Energy thriftiness and metabolic adaptations have had a crucial role in the emergence and spreading of the Homo lineage in the world. A higher-energy demand was required not only for the growing body mass, encephalization and human proliferation, but also for the survival adaptations to the environmental stresses. Because lean body mass lacks the energy-storage capacity required to supply the body’s demands, dedicated fat-storing cells originated. To feed such fat stores, the hominid evolution developed “meat-adaptive” genes to detect, digest and metabolize higher fat diets, and body-fat stores can be affected by lifestyle through hormonal-controlled daily energy balance. In energy surplus conditions, hypertrophy and hyperplasia of adipocytes can occur, with hypertrophic adipocyte signaling both a neo-adipocyte differentiation (leading to hyperplasia) and a local macrophage density (resident + infiltrated macrophages) for fat surplus scavenging. Adiposity-induced inflammation is caused by fat-overstored (hypertrophied) adipocytes that may operate as an overactive endocrine organ secreting an array of pro-inflammatory adipokines that, in combination with resident-macrophage activity and infiltrated blood-recruited, monocyte-derived macrophages, amplify the inflammatory process by spurting pro-inflammatory cytokines into the bloodstream. From an evolutionary perspective, obese humans represent a natural selection overexpressing the “thrifty” genes evolved for efficient food collection and fat deposition intended to help in survival in prolonged periods of famine. However, genetically speaking, obesity is a polygenic multifactorial disorder. Considering the rapidity of obesity-epidemic growth worldwide, epigenetic sets forth the key assumption of the mismatch between our human genome molded over thousands of generations, coping with the unprecedented dietary and physical conditions. Consequently, obesity would be due to our evolutionary-adapted polygenic-charge expressed by a deteriorated lifestyle characterized by high energy-dense food intake coupled with a reduction in caloric expenditure stemming from new mobility-reducing technologies. As a model of lifestyle change (LiSM), our 28-year on-going longitudinal study (“Moving for Health”) has shown effectiveness in the reduction not only of obesity but especially of its comorbidities, in a (10 week to 3 year) length-dependent LiSM. However, a disappointing progressive decrease in compliance with the study has been observed and attributed to the resistance of people to change their actual “obesogenic” lifestyle, basically represented by the individuals’ demand for labor-saving technologies and convenient, affordable, palatable foods.