Abstract 414: Adipose Angiotensin AT2 Receptors Modulate Thermogenesis Though Interactions with Epidermal Growth Factor Signaling

• DOI: 10.1161/hyp.62.suppl_1.a414
• Publication Date: 2021-07-03T09:19:48Z
• Authors: Henry L Keen; Nicole K Littlejohn; Xuebo Liu; Justin L Grobe; Curt D Sigmund
• Keywords: 03 medical and health sciences; 0302 clinical medicine; 3. Good health

The brain renin-angiotensin system (RAS) stimulates resting metabolic rate (RMR) in part through a mechanism involving suppression of the circulating RAS. This effect appears to be mediated loss tonic adipose angiotensin AT2 receptor (AT2R) activation specifically within inguinal fat. Mice with hyperactivity RAS (“sRA” mice, expressing human renin via synapsin promoter and angiotensinogen its own promoter) littermate controls were chronically infused vehicle or AT2R agonist, CGP-42112a (CGP, 90 ng/hr, 8 wk, sc). To identify altered signaling pathways sRA mice their response CGP treatment, total RNA was isolated from tissue transcript abundance quantitated by RNA-Seq (50 bp paired reads sequenced Illumina HiSeq 2000). There significant (P<0.001) change expression 123 genes (n=3) compared (n=3), which generally reversed treatment (n=4). By manual inspection, we observed that 51 these are associated epidermal growth factor (EGF) signaling. Consistent this, Gene Set Enrichment Analysis data demonstrated EGF pathway were, as group, statistically upregulated (P=0.02) suppressed treatment. Therefore, further explore impact increased on RMR isolate potential modulatory this response, wildtype C57Bl/6J male (9 wk) (833 2 sc) without co-infusion CGP. brief infusion caused possible increase (vehicle n=20, 0.173 ± 0.009; 0.192 0.012 kcal/hr, P=0.13), significantly reduced (90 (EGF+CGP n=17, 0.165 0.005, P<0.05 vs alone; alone n=9, 0.156 0.010). Together implicate elevated activity. Further, suggest suppressive upon context Studies utilizing primary cultures underway investigate molecular basis EGF-AT2R interaction.