Publication Date
1-21-2022
Journal
Science Advances
DOI
10.1126/sciadv.abk0185
PMID
35044814
PMCID
PMC8769556
PubMedCentral® Posted Date
1-19-2022
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Abstract
Estrogen receptor–α (ERα) expressed by neurons in the ventrolateral subdivision of the ventromedial hypothalamic nucleus (ERαvlVMH) regulates body weight in females, but the downstream neural circuits mediating this biology remain largely unknown. Here we identified a neural circuit mediating the metabolic effects of ERαvlVMH neurons. We found that selective activation of ERαvlVMH neurons stimulated brown adipose tissue (BAT) thermogenesis, physical activity, and core temperature and that ERαvlVMH neurons provide monosynaptic glutamatergic inputs to 5-hydroxytryptamine (5-HT) neurons in the dorsal raphe nucleus (DRN). Notably, the ERαvlVMH → DRN circuit responds to changes in ambient temperature and nutritional states. We further showed that 5-HTDRN neurons mediate the stimulatory effects of ERαvlVMH neurons on BAT thermogenesis and physical activity and that ERα expressed by DRN-projecting ERαvlVMH neurons is required for the maintenance of energy balance. Together, these findings support a model that ERαvlVMH neurons activate BAT thermogenesis and physical activity through stimulating 5-HTDRN neurons.
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Endocrine System Diseases Commons, Endocrinology, Diabetes, and Metabolism Commons, Medical Sciences Commons
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