Alterations in adequate energy balance maintenance result in serious metabolic disturbances such as obesity. In mammals, this complex process is orchestrated by multiple and distributed neuronal circuits. Hypothalamic and brainstem neuronal circuits are critically involved in the sensing of circulating and local factors conveying information about the energy status of the organism. The integration of these signals culminates in the generation of specific and coordinated physiological responses aimed at regulating energy balance through the modulation of appetite and energy expenditure. In this article, we review current knowledge on the homeostatic regulation of energy balance, emphasizing recent advances in mouse genetics, electrophysiology, and optogenetic techniques that have greatly contributed to improving our understanding of this central process.

Metabolic signals from gut microbes: The gut is a stretchy, glandular, and highly innervated tube packed at its distal end with microorganisms. Disruption of the microbial community can lead to metabolic disorders such as obesity and diabetes. Muller et al. investigated how the microbiota interacts with the enteric nervous system to induce a metabolic outcome. A population of autonomous enteric neurons called CART ⁺ neurons are enriched in the ileum and colon, where most of the microbiota resides. Stimulation or ablation of the CART ⁺ neurons alters blood glucose levels, insulin, and feeding behavior. Furthermore, by manipulating the microbiota, the density of enteric neurons responds plastically in an inducible and reversible manner. Science , this issue p. 314