The Neuroendocrine Control of Energy Balance

When discussing the causes of obesity, it is easy to point fingers at the individual. “Gluttony” and “sloth” after all are two of the seven “deadly sins.” Obese adults and their children are assumed to have “free choice” with regard to food intake and energy expenditure and are therefore “responsible” for their metabolic “fates” (1). But no child chooses to become obese; indeed the quality of life of an obese child is similar to that of children receiving cancer chemotherapy (2). Furthermore, the striking increases in obesity prevalence in 2to 5-year-old children (3) suggest that there are other explanations for the obesity epidemic. Here I explore the biochemical determinants that control energy balance and argue that difficulties in achieving and/or maintaining weight loss reflect the potency of central reinforcement systems, the effects of stress, and the resilience of the body’s adaptive responses. The discovery of leptin in 1994 (4) revealed a complex neuroendocrine axis regulating energy balance. Much of what we know about energy balance is derived from studies of animal models, but clinical studies provide invaluable insights.