School of Arts, Science and Humanities, University of Sao Paulo, Sao Paulo, Brazil.
Department of Biology, Center for Obesity Reversal, Neuroscience Institute, Georgia State University, Atlanta, Georgia, USA.
Physiol Rep. 2023 Mar;11(5):e15621. doi: 10.14814/phy2.15621.
We tested the hypothesis that third ventricular (3V) injections of angiotensin 1-7 (Ang 1-7) increases thermogenesis in brown adipose tissue (BAT), and whether the Mas receptor mediates this response. First, in male Siberian hamsters (n = 18), we evaluated the effect of Ang 1-7 in the interscapular BAT (IBAT) temperature and, using selective Mas receptor antagonist A-779, the role of Mas receptor in this response. Each animal received 3V injections (200 nL), with 48 h intervals: saline; Ang 1-7 (0.03, 0.3, 3, and 30 nmol); A-779 (3 nmol); and Ang 1-7 (0.3 nmol) + A-779 (3 nmol). IBAT temperature increased after 0.3 nmol Ang 1-7 compared with Ang 1-7 + A-779 at 20, 30, and 60 min. Also, 0.3 nmol Ang 1-7 increased IBAT temperature at 10 and 20 min, and decreased at 60 min compared with pretreatment. IBAT temperature decreased after A-779 at 60 min and after Ang 1-7 + A-779 at 30 and 60 min compared with the respective pretreatment. A-779 and Ang 1-7 + A-779 decreased core temperature at 60 min compared with 10 min. Then, we evaluated blood and tissue Ang 1-7 levels, and the expression of hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) in IBAT. Male Siberian hamsters (n = 36) were killed 10 min after one of the injections. No changes were observed in blood glucose, serum and IBAT Ang 1-7 levels, and ATGL. Ang 1-7 (0.3 nmol) increased p-HSL expression compared with A-779 and increased p-HSL/HSL ration compared with other injections. Ang 1-7 and Mas receptor immunoreactive cells were found in brain regions that coincide with the sympathetic nerves outflow to BAT. In conclusion, 3V injection of Ang 1-7 induced thermogenesis in IBAT in a Mas receptor-dependent manner.
我们检验了这样一个假设,即血管紧张素 1-7(Ang 1-7)在第三脑室(3V)的注射可以增加棕色脂肪组织(BAT)的产热作用,并且 Mas 受体是否介导这种反应。首先,在雄性西伯利亚仓鼠(n = 18)中,我们评估了 Ang 1-7 对肩胛间 BAT(IBAT)温度的影响,并使用选择性 Mas 受体拮抗剂 A-779,评估了 Mas 受体在这种反应中的作用。每个动物接受 3V 注射(200nL),间隔 48 小时:生理盐水;Ang 1-7(0.03、0.3、3 和 30nmol);A-779(3nmol);和 Ang 1-7(0.3nmol)+A-779(3nmol)。与 Ang 1-7+A-779 相比,0.3nmol Ang 1-7 在 20、30 和 60 分钟后增加了 IBAT 温度。此外,0.3nmol Ang 1-7 在 10 和 20 分钟时增加了 IBAT 温度,而在 60 分钟时则降低了。与预处理相比,A-779 在 60 分钟时,Ang 1-7+A-779 在 30 和 60 分钟时降低了 IBAT 温度。与 10 分钟相比,A-779 和 Ang 1-7+A-779 在 60 分钟时降低了核心温度。然后,我们评估了血液和组织中的 Ang 1-7 水平,以及激素敏感脂肪酶(HSL)和脂肪甘油三酯脂肪酶(ATGL)在 IBAT 中的表达。雄性西伯利亚仓鼠(n = 36)在其中一次注射后 10 分钟被处死。血糖、血清和 IBAT Ang 1-7 水平以及 ATGL 没有变化。与 A-779 相比,Ang 1-7(0.3nmol)增加了 p-HSL 的表达,并增加了 p-HSL/HSL 比率。在与 BAT 交感神经传出相一致的脑区发现了 Ang 1-7 和 Mas 受体免疫反应细胞。总之,3V 注射 Ang 1-7 以 Mas 受体依赖的方式诱导了 IBAT 的产热作用。