Central regulators of food intake

Purpose of review Obesity is a major public health problem and is associated with significant morbidity and mortality from coronary heart disease and type 2 diabetes. The population is becoming increasingly obese, yet for individuals weight is regulated within a narrow range. This regulation depends on the balance between energy intake (in the form of food) and energy expenditure. Thus in order to regulate weight and energy stores, the body must be able to control food intake accurately. Recently there has been a remarkable increase in our understanding of the molecular mechanisms regulating food intake and energy homeostasis. Recent findings There is increased understanding of the central pathways by which known neurotransmitters affect food intake. These include peptides expressed in hypothalamic nuclei, but other brain regions including brain stem, amygdala and nucleus accumbens, are also important. Further central transmitters have been identified, such as that encoded by the gene identified in mice with the mahoganoid mutation, and roles for known transmitters have been elucidated, such as endocannabinoids and acetylcholine. There is new evidence regarding peripheral modulation of these pathways including the role of ghrelin as an initiator of feeding, and peptide YY as a medium-term satiety signal. Summary Complex central circuitry controls food intake and energy expenditure. Circulating factors that modulate these pathways have appetite stimulation or satiety effects. These are potentially important targets for therapy in obesity. Single-gene models of obesity in animals are important in understanding these pathways, however human clinical correlates for genetically determined obesity are uncommon.