Obesity is the presence of excessive amount of adipose tissue. The excessive adipose tissue causes increased blood pressure, hepatic lipid synthesis, insulin resistance, and susceptibility to certain cancers. The anatomic location of the extra body fat has an important effect on the occurrence of these morbidities. Fat located in the intra-abdominal depot appears to convey greater metabolic risk than that in subcutaneous sites. The degree of fatness at which medically significant changes in these quantitative phenotypes occur is variable among individuals and, to some extent, ethnic groups. For example, obesity conveys greater risk of type 2 diabetes in Hispanics, African-Americans and Asians than in Caucasians. Advanced chronologic age may mitigate some of the adverse consequences of an otherwise excessive amount of body fat. For these reasons, no specific absolute amount or fractional content of body fat can be defined as pathologic for all individuals. Finally, adiposity and diminished “metabolic fitness” are not necessarily synonymous. Thus, individuals with high degrees of relative fatness can be physically fit and without apparent metabolic consequence of their adiposity if maintained—with exercise—at sufficient levels of aerobic and strength fitness. For actuarial and public health purposes, recently promulgated World Health Organization Expert Guidelines suggest that overweight and obesity be defined by body mass indices (BMI, a surrogate for adiposity, = Wt(kg)/[Ht(m)]2) of 25 and 30, respectively.
Studies of the concordance rates for adiposity among mono- and dizygous twins, and among adoptive children and their family members, and segregation and linkage and association studies, all point to a substantial contribution of genes to the determination of body composition in humans. Relatively rare instances of heritable syndromic obesity (Prader-Willi, Bardet-Biedl, etc.) are well known. More recently, rare mutations of human orthologs of some of the rodent single-gene obesity mutations have been identified (LEP, LEPR), as well as mutations in other genes that play a role in the control of body fat (e.g., POMC, MC4R, and PPARG). However, human obesity is complex and multigenic, with the penetrance of responsible genes showing strong dependence on environmental circumstance. The accelerating prevalence of obesity throughout the world, and especially in developed countries, must be the result of ever more “propitious” environmental circumstances that include high-caloric density foods and labor-saving technologies. The relevant genes determine an individual's adiposity relative to peers in the same environment.
Experiments in animals and humans point to a dependence of ingestive behavior, reproductive function, somatic growth, and carbohydrate homeostasis on the size of somatic fat stores. Body fat content is “defended” by a complex, coordinated series of metabolic and behavioral responses to reduction of body fat stores below a threshold that is determined by genetic and developmental factors. Clinical evidence of the existence of such regulatory mechanisms is the remarkable long-term constancy of body weight in adults. The average weight gain of 20 pounds between ages 25 and 55 years, considered in the context of energy intake of approximately 900,000 kcal per ...