An interoceptive circuit regulating energy balance

Feeding is an innate, context-dependent behaviour that is guided by numerous interoceptive inputs, including leptin, a hormone released by white adipose tissue that lowers food intake. The circuit that links this and other interoceptive inputs to consummatory behaviours is incompletely understood, although specific nuclei such as the ventromedial hypothalamus (VMH) are known to be crucial. Now, Kosse et al. characterize a feeding circuit that links leptin via the hypothalamus to brainstem motor circuits that control the jaw.

This study emerged from investigations by the authors into the circuits that underlie the marked increase in feeding thatoccurs following alterations in brain-derived neurotrophic factor (BDNF) or its receptor TrkB in mice or humans. The authors investigated the function of BDNF-expressing VMH (VMH^BDNF) neurons in fed, fasted and obese mice (with obesity induced by a high-fat diet). In obese mice (compared with chow-fed controls), BDNF neurons in the VMH, but not elsewhere, showed higher FOS expression, a proxy for neuronal activation. Ablation of these neurons in obese mice led to substantial weight gain compared to intact obese mice, indicating that these neurons normally restrict overfeeding. Consistent with this, optogenetic inhibition of VMH^BDNF neurons increased food intake in lean and obese mice, and administration of leptin, which reduces food intake, increased VMH^BDNF neuronal activity. Using a combination of monosynaptic tracing, in situ hybridization and optogenetics, the authors showed that VMH^BDNF neurons receive inputs from leptin-receptor-expressing neurons in the arcuate nucleus, a key interoceptive input area, thus revealing a pathway by which body weight-related interoceptive information reaches the VMH.