Discrete TrkB-expressing neurons of the dorsomedial hypothalamus regulate feeding and thermogenesis

Abstract

Mutations in the TrkB neurotrophin receptor lead to profound obesity in humans, and expression of TrkB in the dorsomedial hypothalamus (DMH) is critical for maintaining energy homeostasis. However, the functional implications of TrkB-expressing neurons in the DMH (DMHTrkB) on energy expenditure are unclear. Additionally, the neurocircuitry underlying the effect of DMHTrkB neurons on energy homeostasis has not been explored. In this study, we show that activation of DMHTrkB neurons leads to a robust increase in adaptive thermogenesis and energy expenditure without altering heart rate or blood pressure, while silencing DMHTrkB neurons impairs thermogenesis. Furthermore, we reveal neuroanatomically and functionally distinct populations of DMHTrkB neurons that regulate food intake or thermogenesis. Activation of DMHTrkB neurons projecting to the raphe pallidus stimulates thermogenesis and increased energy expenditure, whereas DMHTrkB neurons that send collaterals to the paraventricular hypothalamus and preoptic area inhibit feeding. Together, our findings provide evidence that DMHTrkB neuronal activity plays an important role in regulating energy expenditure and delineate distinct neurocircuits that underly the separate effects of DMHTrkB neuronal activity on food intake and thermogenesis.Brief summaryThis study shows that TrkB-expressing DMH neurons stimulate thermogenesis through projection to raphe pallidus, while inhibiting feeding through collaterals to paraventricular hypothalamus and preoptic area.

The Pleiotropic Potential of BDNF beyond Neurons: Implication for a Healthy Mind in a Healthy Body

“…Energy consumption mediated by thermogenesis and physical activity was furthermore induced by the activation of neurons that express TrkB in the DMH. This recent study revealed distinct neuronal populations expressing TrkB which create neurocircuitry by projections to several brain regions (raphe pallidus, PVH and preoptic area) to accurately manage energy expenditure and food intake [36]. www.videleaf.com Genetic disorders causing BDNF haploinsufficiency or TrkB inactivation provide direct evidence for the understanding of the role of BDNF in the regulation of energy balance in humans.…”