Abstract
The prevalence of obesity has increased substantially in the past 3 decades and is projected to increase further in the years ahead. It increases the risk of diabetes mellitus, dyslipidemia, hypertension, cardiovascular disease, sleep apnea, nonalcoholic hepatic steatosis, gallbladder disease, osteoarthritis, and cancer. The prevention and treatment of obesity is, therefore, a leading challenge facing public health and medicine in the 21st century. Two stereotypes have dominated thinking in public health, medicine, and the media about obesity. The first stereotype is that the recent surge in prevalence of obesity reflects almost entirely environmental and psychological factors and excludes an important contribution of genetic biological factors. The second stereotype is that obesity should and can be treated primarily by diet and behavioral modification. In this review, I challenge these tenets. I summarize evidence for a strong genetic neurobiological contribution to adiposity and body weight and assert that common human obesity is, like essential hypertension, a complex multifactorial disease where genetic factors promote sensitivity or resistance to obesity in a toxic environment. This concept of a genetic resistance versus sensitivity to obesity helps explain why many people remain thin in a toxic environment whereas others develop profound obesity. I then discuss evidence that dietary therapy for obesity generally fails to achieve weight loss maintenance. There is mounting indication that the high rate of relapse from weight loss during dietary therapy occurs because of compensatory biological adaptations that promote lack of compliance and effectiveness. Relapse from weight loss during dietary therapy is not caused simply by lack of discipline and will power. Finally, I briefly discuss the alternatives to dietary and behavioral therapy, namely bariatric surgery and pharmacotherapy. As a prelude to my critique of dietary therapy, I begin with a discussion of the role of genetic neurobiological factors in obesity. The surge …
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