The absence of predation led to a change in the population distribution of body fatness due to random mutations and genetic drift. Speakman 2 argues that around 2 million years ago, predation was removed as a significant factor by the development of social behaviors, weapons, and fire. 1 This hypothesis of the ‘thrifty genotype’ has, however, recently been challenged by Speakman 2 who offers an alternative explanation called the ‘predation release’ hypothesis. However, what was an asset during evolution has become a liability in the current ‘pathoenvironment’ or ‘obesogenic’ environment. Throughout evolution, humans and animals have evolved redundant mechanisms promoting the accumulation of fat during periods of feast to survive during periods of famine. The concept of metabolic flexibility and its impact on body weight regulation is also presented. If sustained over time, such an increase in energy intake cannot be detected by available methods, but may cause meaningful increases in body weight. This drive for balance may in turn cause increased energy intake when consuming a diet high in fat and low in carbohydrate. Because of the small storage capacity for carbohydrate and its importance for metabolism in many tissues and organs, carbohydrate balance must be maintained at a given level. In this study, we also review evidence that carbohydrate balance may represent the potential signal that regulates energy homeostasis by impacting energy intake and body weight. Clearly, the data suggest a strong genetic influence on body weight regulation implying a normal physiology in an ‘obesogenic’ environment. Additionally, large variability in weight change is observed when energy surplus is imposed experimentally or spontaneously. However, this equilibrium seems to be particularly difficult to achieve in individuals with low fat oxidation, low energy expenditure, low sympathetic activity or low levels of spontaneous physical activity, as in addition to excess energy intake, all of these factors explain the tendency of some people to gain weight. For weight maintenance, not only does energy intake have to match energy expenditure, but also macronutrient intake must balance macronutrient oxidation. Therefore, multiple and complex mechanisms have evolved to regulate energy intake and expenditure to maintain body weight. Energy homeostasis is critical for the survival of species.
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