biostudies-literatureSavani RHNational Institute of Diabetes and Digestive and Kidney DiseasesWhitehall FoundationNational Institutes of HealthRobert Wood Johnson Foundation114070https://www.ebi.ac.uk/biostudies/studies/S-EPMC12704261biostudies-literatureUnknown28(12)Energy homeostasis is tightly regulated to ensure metabolic health in uncertain environments. Neurons expressing the glucagon-like peptide-1 receptor (GLP-1R) contribute to maintaining body weight, but how their activity is regulated according to energy state remains unclear. Here, we investigated the function and cellular dynamics of GLP-1R-expressing neurons of the paraventricular hypothalamus (PVH^GLP-1R) during food consumption, providing strong evidence of their ability to bidirectionally control feeding. Elevating intracellular signaling through 3',5'-cyclic adenosine monophosphate (cAMP), the major pathway downstream of GLP-1R, suppressed feeding. Using two-photon calcium imaging, we observed heterogeneous single-cell responses to ingestion that occurred regardless of eneriScienceIndividual paraventricular hypothalamic GLP-1R neurons track ingestion across energy states.PMC1270426174260R01DK136641R01DK1314522022-12-051Lu YSavani RHYang MLe TPang ZPRossi MAWang LPark EfalseIndividual paraventricular hypothalamic GLP-1R neurons track ingestion across energy states.Energy homeostasis is tightly regulated to ensure metabolic health in uncertain environments. Neurons expressing the glucagon-like peptide-1 receptor (GLP-1R) contribute to maintaining body weight, but how their activity is regulated according to energy state remains unclear. Here, we investigated the function and cellular dynamics of GLP-1R-expressing neurons of the paraventricular hypothalamus (PVH^GLP-1R) during food consumption, providing strong evidence of their ability to bidirectionally control feeding. Elevating intracellular signaling through 3',5'-cyclic adenosine monophosphate (cAMP), the major pathway downstream of GLP-1R, suppressed feeding. Using two-photon calcium imaging, we observed heterogeneous single-cell responses to ingestion that occurred regardless of ener2025-01-01T00:00:00Z2025 Dec2026-07-15T06:34:04.042Z2026-06-30T03:20:42.048ZS-EPMC127042614140383110.1016/j.isci.2025.114070