Angiotensin AT_1A receptor signal switching in Agouti-related peptide neurons mediates metabolic rate adaptation during obesity.

ABSTRACT: Resting metabolic rate (RMR) adaptation occurs during obesity and is hypothesized to contribute to failed weight management. Angiotensin II (Ang-II) type 1 (AT_1A) receptors in Agouti-related peptide (AgRP) neurons contribute to the integrative control of RMR, and deletion of AT_1A from AgRP neurons causes RMR adaptation. Extracellular patch-clamp recordings identify distinct cellular responses of individual AgRP neurons from lean mice to Ang-II: no response, inhibition via AT_1A and Gαi, or stimulation via Ang-II type 2 (AT₂) receptors and Gαq. Following diet-induced obesity, a subset of Ang-II/AT_1A-inhibited AgRP neurons undergo a spontaneous G-protein "signal switch," whereby AT_1A stop inhibiting the cell via Gαi and instead

SUBMITTER: Balapattabi K 

PROVIDER: S-EPMC10530419 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature