Etiology and pathogenesis
Obesity results from an energy imbalance. Experimental evidence shows that obesity develops when energy intake exceeds energy expenditure, and weight is lost when energy expenditure exceeds energy intake. Nevertheless, controversies remain over the specific mechanisms that lead to this imbalance. Obese children do not appear to have lower metabolic rates or lower energy expenditures than nonobese children. Obese children do tend to underestimate their food intake and overestimate their physical activity compared to nonobese children, although data are inconsistent on whether obese children actually consume more calories (ie, eat more) than their nonobese peers. However, methods used to measure energy intake and expenditure have limited accuracy. Extremely small energy discrepancies can lead to large changes in body weight over time. For example, one extra 12-ounce can of regular soda per day is the caloric equivalent of about 15 pounds of excess weight gain over the course of a year.

The genetic contribution to obesity is receiving increased attention.

Some data have even been interpreted to suggest that heredity explains nearly all obesity. However, a careful look at the evidence suggests that the role of genes in the etiology of obesity is more complex. Many candidate obesity genes have been identified in rodents. However, most linkage studies have yet to offer strong evidence of a role in human obesity, and the human mutations that have been identified to date are unlikely responsible for the most common forms of obesity. Although body fatness is correlated in families, the strength of these correlations is much greater in the normal weight range than among the obese. This and other methodologic factors may account for exaggerated estimates of the genetic contribution to obesity in twin studies. Some of the most informative evidence comes from experimental energy balance manipulations among adult twin pairs. These studies confirm a significant hereditary component to changes in body composition. However, even in controlled experimental settings, heredity accounts for a maximum of only about 25% of the variation in weight (and fat) gain and loss. As a result, 75% or more is left to be explained by nongenetic influences. Heredity appears to play its primary role in the susceptibility to obesity, but environmental and behavioral influences determine how genetic susceptibility is expressed.

The timing of weight gain also may play a role in the onset and persistence of obesity. At least three critical periods occur during childhood when the onset of obesity is more likely to persist into adulthood. These include the prenatal period, the period of normal adiposity rebound (ie, about 5 to 7 years of age), and the early adolescent years associated with puberty. All three periods are characterized by normal changes in the growth and distribution of adipose tissue. Overnutrition (ie, more calorie consumption than calorie expenditure) during any of these periods may entrain an obese physiology. Thus, preventive interventions may be more successful if they specifically target these periods.