Neuroendocrinology of Energy Balance

Abstract

In the past decades, the spiraling obesity epidemic has renewed the interest of basic scientists in the control of hunger and satiety, food intake and energy expenditure, and body weight regulation by the central nervous system. The discovery of the adipose-derived satiety hormone, leptin, in 1994 greatly advanced the neuroscience of obesity by enabling detection and characterization of the – largely hypothalamic – neurocircuits that underpin feeding behavior and energy balance regulation. A number of circulating factors that affect the energy balance at the central level have subsequently been discovered in the adipose organ, the gastrointestinal tract, and the endocrine pancreas or their mechanisms of action have been characterized. Although several major pieces of the picture are still missing, the available data suggest that energy balance homeostasis is achieved at the central level by hypothalamic and brainstem neurocircuits which integrate metabolic stimuli with cognitive, hedonic, and emotional cues, regulating energy use and storage and body weight homeostasis through behavioral, autonomic, and endocrine responses. These extremely complex and closely integrated neurocircuits are mainly peptidergic and give rise to a highly redundant system. They operate continuously in response to stimulatory or inhibitory hormonal and metabolic inputs coming from the periphery of the body through the circulation. Such crosstalk between “center” and “periphery” is currently a major area of energy balance research. Its elucidation is expected to provide in the near future novel druggable targets for the effective treatment of obesity and related diseases in humans.