Central Ang 1‐7 Modulates Lipolysis and Thermogenesis in Adipose Tissue.

Abstract

Angiotensin 1‐7 (Ang 1‐7) attenuates metabolic dysfunction and increases sympathetic drive. We investigated the effect of third ventricular (3V) injection of Ang 1‐7 on lipolytic and thermogenic activities of adipose tissue (AT). Siberian hamsters (Experiment 1, n=18) had 3V cannulae implanted, interscapular brown AT (IBAT) temperature transponders and an intraperitoneal temperature probe. Each animal received 3V injections (200 nl) with 48h intervals: saline (S), 0.3 nmol Ang 1‐7, 3 nmol A‐779 (Mas receptor antagonist) and 0.3 nmol Ang 1‐7 + 3 nmol A‐779. IBAT temperature increased after Ang 1‐7 at 10 and 20 min, decreased after A‐779 at 60 min, and was higher after Ang 1‐7 than Ang 1‐7 + A‐779 at 20, 30 and 60 min. A‐779 and Ang 1‐7 + A‐779 decreased core temperature at 60 min compared with 10 min (p蠄0.05). In the Experiment 2, the animals (n=36) were killed 10 min later after a single injection. Blood Ang 1‐7 and glucose did not change, but Ang 1‐7 injection increased free fatty acids compared with S and A‐779, and serum glycerol compared with S (p蠄0.05). Ang 1‐7 increased p‐HSL expression compared with A‐779 (IBAT), increased p‐HSL/HSL ratio compared with other injections (IBAT) and with S in retroperitoneal white AT (RWAT; p蠄0.05), but did not change in epididymal and inguinal AT (EWAT and IWAT). ATGL was not changed in IBAT, RWAT or EWAT, but was reduced after Ang 1‐7 and A‐779 injections compared with S in IWAT (p蠄0.05). UCP‐1 protein expression did not change in IBAT. In conclusion, central Ang 1‐7 increased IBAT thermogenesis and increased cellular markers of lipolysis in IBAT and RWAT in a Mas receptor‐dependent manner, according to p‐HSL/HSL ratio. Supported by FAPESP (13/03083‐4) to FSE and NIH R37 DK35254 to TJB.