Figure 1. Model to explain compensatory adjustments of caloric intake and expenditure in response to changes in body fat content. Leptin and insulin are peripheral adiposity signals that circulate in proportion to the amount of body fat and act in the hypothalamus to stimulate catabolic effector pathways while inhibiting anabolic pathways. These pathways exert opposing effects on energy balance (the difference between calories consumed and expended), which, in turn, determines the amount of body fat. CNS indicates central nervous system. Reprinted with permission from Nature (Schwartz et al¹⁰), 2000, Macmillan Publishers Ltd.