Paraventricular nucleus–locus coeruleus VGlut2 neural circuit regulates energy metabolism in mice

Abstract

Abstract The role of the central nervous system in energy homoeostasis remains unclear. This study examined the role of VGlut2-expressing neurons in the paraventricular nucleus of the hypothalamus (PVH VGlut2 ) and their downstream circuits in the regulation of energy homoeostasis. Long-term high-fat diet (HFD) disrupts energy balance and compensatorily activates PVH VGlut2 neurons that innervate interscapular brown adipose tissue (iBAT). These neurons are inhibited during food consumption, suggesting their involvement in feeding and energy metabolism regulation. Activation of PVH VGlut2 neurons reduces food intake and enhances iBAT thermogenesis. Further, optogenetic PVH VGlut2 → locus coeruleus (LC) circuit activation inhibited feeding and elevated iBAT temperature, which was blocked by sympathetic nerve denervation. Long-term chemogenetic PVH VGlut2 → LC neural circuit activation ameliorates HFD-induced obesity and insulin resistance. The PVH VGlut2 → LC circuit integrates feeding inhibition and peripheral thermogenesis signals to regulate energy metabolism, offering potential intervention targets for obesity and other energy homoeostasis disorders.

Affiliated Institutions

• Inner Mongolia Agricultural University CN
• Inner Mongolia Academy of Agricultural & Animal Husbandry Sciences CN

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