Abstract P072: Adipocyte AT 2 Receptor Suppresses UCP1 Transcription and Thereby Resting Metabolic Rate

• DOI: 10.1161/hyp.66.suppl_1.p072
• Publication Date: 2022-03-20T01:28:34Z
• Authors: Nicole K Littlejohn; Benjamin J Weidemann; Nicole A Pearson; Meghan C Naber; Matthew J Potthoff; Aloysius Klingelhutz; Curt D Sigmund; Justin L Grobe
• Keywords: Thermogenin

The renin-angiotensin system (RAS) contributes to energy balance through opposing actions in the brain and periphery. We hypothesize that tissue- receptor-specific RAS modulation may represent a novel therapeutic approach obesity. Transgenic “sRA” mice exhibit brain-specific hyperactivity expression of human renin neurons (synapsin promoter) angiotensinogen via its own promoter. Previously we documented sRA suppressed circulating RAS, an elevated resting metabolic rate (RMR) is sensitive replacement angiotensin II or AT 2 receptor (AT R) agonist, CGP-42112a (CGP, 100 ng/kg/min, s.c.). robust specific elevation uncoupling protein-1 (UCP1) glucose uptake inguinal white adipose tissue (iWAT). Chronic infusion R (CGP) into increased weight gain normalized RMR fat UCP1, but had no effect on food intake digestive efficiency. suppression by CGP was not mediated attenuation sympathetic nervous activity (SNA, measured multifiber nerve recordings), leading hypothesis action adipocyte suppresses sensitivity SNA. Cultured primary mouse adipocytes were isolated from iWAT, norepinephrine (NE, 1 nM) treatment induced UCP1 mRNA (597 -fold vehicle, P<0.05), however this induction attenuated with co-treatment (10 nM, 0.2 NE alone, P<0.05). In adipocytes, activation also prevented NE-induced increase mRNA. additionally significantly lipolysis (measured free glycerol media; (vehicle= 15.9 ug/mL; NE= 70.8 + CGP=64.7 ug/mL). These data support suppressive upon specifically expression, lipolysis, within subcutaneous adipocytes. Ongoing studies are examining transcriptional regulation activation.