Adiposity signals and the control of energy homeostasis

Abstract

Recent technologic innovations have enabled probing the workings of individual cells and even molecules. As a result, our knowledge of the biological controls over eating and the regulation of body adiposity is increasing at a rapid pace. We review the evidence that food intake is controlled by separate but interacting groups of molecular signals. One group, termed satiety signals, are proportional to what is being consumed and help to determine meal size. Cholecystokinin is the best known of these, and its premeal administration causes a dose-dependent reduction of meal size. In and of itself, however, cholecystokinin (and other satiety signals) has little impact on body-fat stores. The second group, termed adiposity signals, circulate in proportion to body adiposity and enter the brain, where they interact with satiety signals in the brainstem and hypothalamus. Insulin and leptin are the best known of these adiposity signals, and the administration of either into the brain causes a dose-dependent reduction of both food intake and body weight. Within the brain, parallel but opposing pathways originating in the hypothalamic arcuate nuclei integrate adiposity signals with satiety signals. Those with a net anabolic effect increase food intake and reduce energy expenditure and are represented (among many such signals) by neuropeptide Y; those with a net catabolic effect decrease food intake and energy expenditure and are represented by brain melanocortins. This complex regulatory mechanism allows individuals to adapt their feeding schedule to idiosyncratic environmental constraints, eating whenever it is desirable or possible. Body-weight regulation occurs as adiposity signals alter the efficacy of meal-generated satiety signals.