Richard L. Atkinson
Virginia Commonwealth University, Obetech Obesity Research Center, 800 East Leigh St., Suite 50,
Richmond, VA 23219, USA
There is a worldwide epidemic of obesity that is creating great health problems for individuals and massive economic costs for governments. More than 68% of American adults are overweight or obese. Many government and professional society guidelines for the treatment of obesity state that “diet and exercise are the primary treatment of obesity.” If the search terms “obesity and lifestyle and treatment and human” are used in PubMed, there are 8819 references. None have shown significant long term success of lifestyle treatment of obesity – the 5 year failure rate is >95%. It seems highly unlikely that the 8820th study of lifestyle is suddenly going to prove successful. Only in 2013 did the American Medical Association adopt a statement that obesity is a “disease.” Before the founding of the American Obesity Association, a lay advocacy group, in 1995, the NIH spent about $30 million on obesity research out of a total budget of about $12 billion. This was less than 1% of the budget for a disease affecting almost 30% of American adults at that time. Currently, the NIH states on its website that it spends about $857 million on obesity research, but since the total budget figure is inflated by 5 fold, the true expenditure probably is about $171 million. A quite significant percentage of this amount is spent on lifestyle research. In contrast to more established diseases, the early research into obesity has not focused on basic science, but on treatment (e.g., $220 million for the “LOOK AHEAD” trial). We are in our infancy of the understanding of obesity. Since pre-history, humans have thought they knew the etiology of obesity – too much diet and too little exercise. It seems logical, but just because a perturbation affects a variable, does not mean that it is the cause of the variable. It seems quite possible that diet and exercise account for only a very small percentage of obesity. There is no doubt that body weight, or at least body fat, are regulated by the body. Why some people regulate at a high percentage of body fat vs others is not clear. Recent research has identified a number of etiologies of obesity that are NOT the “Big Two” of diet and exercise. This talk will summarize the research on some of these alternate etiologies of obesity and focus on several that may be responsible for large portions of obesity. Genetic factors are very important. At least 60 genes have been shown to contribute to or prevent obesity. Calculating the factorial (60 x 59 x 58, etc.), there are more combinations of genes for obesity than there are people on Earth. Next is virus-induced obesity. Human adenovirus 36 (Adv36) causes obesity in animals and in multiple countries that have been studied, about 30% of obese humans have been infected compared to about 10%-20% of non-obese humans. Scientists have postulated that Adv36 first appeared in the 1970s, just before the prevalence of obesity dramatically increased across the world. Another etiology of obesity that is being recognized as a major contributor to the epidemic are presumably epigenetic factors affecting women of child bearing age. If a woman has the following factors before and during pregnancy, the risk of obesity in her child is 20-40 fold higher than if none of the factors are present: obese at conception, increased weight gain, smoking, eating a high fat or high carbohydrate diet, lack of exercise, older age, taking certain drugs, and perhaps one of the most important, developing gestational diabetes during pregnancy. Almost all of these factors may be avoided or removed, and some evidence suggests that this will prevent a great deal of obesity in her offspring. Other factors that may play a role in causing obesity are certain drugs that are taken much more commonly in the last 30 years, certain industrial pollutants in the environment, and alteration of gut microbiota by changes in the diet favoring processed or refined foods and beverages. The etiology of obesity is so complex that a concerted effort must be made to identify basic biochemical and molecular factors leading to obesity. This information must be used to identify new drugs for treating obesity. Finally, in contrast to most “cookie cutter” treatment of obesity today, individualized treatment must be developed. No two patients are alike and it seems likely that obesity treatment options will be very numerous in the future.