Brain glucose sensing in homeostatic and hedonic regulation

•Glucose-sensing cells are located in different nuclei in the brainstem and hypothalamus.•They control autonomic nervous activity, peripheral organ function, and hormone secretion.•They also control the hedonic value of food through interaction with the mesolimbic dopamine system.•Dysfunction of central glucose sensing may precede and cause development of obesity and diabetes.

Glucose homeostasis as well as homeostatic and hedonic control of feeding is regulated by hormonal, neuronal, and nutrient-related cues. Glucose, besides its role as a source of metabolic energy, is an important signal controlling hormone secretion and neuronal activity, hence contributing to whole-body metabolic integration in coordination with feeding control. Brain glucose sensing plays a key, but insufficiently explored, role in these metabolic and behavioral controls, which when deregulated may contribute to the development of obesity and diabetes. The recent introduction of innovative transgenic, pharmacogenetic, and optogenetic techniques allows unprecedented analysis of the complexity of central glucose sensing at the molecular, cellular, and neuronal circuit levels, which will lead to a new understanding of the pathogenesis of metabolic diseases.