Obesity, the Obesity Epidemic, and Metabolic Dysfunction: The Conundrum Presented by the Disconnect between Evolution and Modern Societies

Abstract

Currently, there is an obesity epidemic in the developed world, with both adults and children being affected. The consequences of this epidemic on health and health outcomes have impact at multiple levels, and it is increasing. The basis for this epidemic, which appears to have emerged with significance ~40 - 50 years ago, is unknown but is believed by many to have much of its basis in poor diets and inactivity/sedentary behaviour. Analysis of the human genome has revealed >100 loci which exhibit risk for development of obesity. Why there are so many loci, and how they benefited humans evolutionarily are unknown. In spite of these limitations, there are urgent needs for effective short-term interventions to assist those with obesity, as well as longer-term needs to effectively prevent development of obesity. For the former, personalized exercise programs, use of prebiotics, optimal nutrition and surgical interventions can be effective for some individuals but more interventions that address cause are also needed. For longer term solutions more detailed genetic and epigenetic understanding of risk will be required. An attractive speculation is that the genomic risk factors for obesity (>100 identified) have been retained evolutionarily to address acute metabolic needs and current conditions have converted such risks to a chronic state, making reversal more difficult and with more consequences, including possible epigenetic modifications of risk genes. Other contributing factors to chronic obesity could also relate to chemical disruptors in the environment over the past 50+ years which may impact metabolic regulation via the established risk genomic risk factors or new variants. Therefore, to effectively control this high impact epidemic of obesity likely requires a more detailed genetic and epigenetic analysis of families with obesity and analysis of isolated populations, as well as a more thorough investigation of chemicals capable of being metabolic disruptors in this regard. Thus, the long-term solution(s) to the obesity epidemic will require a concerted multidisciplinary approach that may be more complex than just becoming more active and avoiding sedentary behavior.