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.
Highlights
Obesity is considered an epidemic in the developed world, with the United States a country with >30% of the population obese based on body mass index (BMI), and an epidemic further impacted by the current pandemic [3, 4]
Having genetic/epigenetic tools to enhance food storage and retain the energy content of foods to successfully get through shortages may be a very different scenario from development of chronic obesity which may convert the multitude of genetic risk factors into the chronic form with associated acute-to-chronic modifications which make turning back either difficult or not possible! In other chronic diseases, the development of a chronic disease or state is often accompanied by epigenetic alterations that can change the landscape dramatically [17,18,19]
A key to perhaps better understanding regarding the WHY of the obesity epidemic is to examine the differences between the modern situation and those that likely contributed to the risks that were acquired during evolution
Summary
Obesity is considered an epidemic in the developed world, with the United States a country with >30% of the population obese based on body mass index (BMI) (discussed in [1, 2]), and an epidemic further impacted by the current pandemic [3, 4]. The general conclusion is that much of the epidemic is blamed on poor nutrition (reliance on diets containing too much unhealthy fat and sugar) and sedentary behavior This interpretation is complicated by the large number (>100) of genetic risk factors for obesity that have been reported [8,9,10], and epigenetic influences appear to be drivers, even across generations via inheritance of risk or within generations [11, 12]. It should be noted that many individuals who lose large amounts of weight while on diets go on to often regain the weight, even when trying to slow down the process This lack of success has frustrated both the medical community focused on obesity and its consequences, and obese individuals, many of whom would prefer a “quick fix” from the pharma industry rather than the perhaps tougher behavior and lifestyle modification route which may not yield long term benefit. It remains to be confirmed that behavior and lifestyle are the only variables at play
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