Angiotensin 1-7 stimulates brown adipose tissue and reduces diet-induced obesity
Angiotensin 1-7 stimulates brown adipose tissue and reduces diet-induced obesity
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DOI：
10.1152/ajpendo.00192.2017
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发表时间：
2018-02-01
影响因子：
5.1
通讯作者：
Hosoi, Hajime
中科院分区：
文献类型：
--
作者：
Morimoto, Hidechika;Mori, Jun;Hosoi, Hajime
肾素-血管紧张素系统是代谢的关键调节因子，血管紧张素1-7 （Ang 1-7）肽具有有益的作用。我们假设Ang 1-7的抗肥胖作用与刺激棕色脂肪组织（BAT）有关。我们通过植入微渗透泵给高脂饮食（HFD）诱导的肥胖小鼠注射Ang 1-7 (0.54 mg kg(-1) day(-1))，持续28天。Ang 1-7治疗降低了体重，上调了产热，改善了受损的葡萄糖稳态，而不影响食物消耗。此外，Ang 1-7处理增加了BAT，增加了UCP1、PRDM16和prohitin的表达。PRDM16表达的改变与AMPK和mTOR磷酸化的增加相关。Ang 1-7处理在不改变UCP1表达的情况下提高皮下白色脂肪组织的生热作用。这些变化发生在hfd喂养小鼠的BAT中脂质积累减少的背景下，伴随着激素敏感脂肪酶的磷酸化和perilipin表达减少，胰岛素信号得以保留。这些数据表明，Ang 1-7诱导棕色脂肪细胞分化，导致饮食性肥胖的产热上调和代谢谱改善。增强Ang 1-7的作用是一种很有希望的治疗方法，可以增加BAT并减少与饮食引起的肥胖相关的代谢并发症。
The renin-angiotensin system is a key regulator of metabolism with beneficial effects of the angiotensin 1-7 (Ang 1-7) peptide. We hypothesized that the antiobesity effect of Ang 1-7 was related to the stimulation of brown adipose tissue (BAT). We administered Ang 1-7 (0.54 mg kg(-1) day(-1)) for 28 days via implanted micro-osmotic pumps to mice with high-fat diet (HFD)-induced obesity. Ang 1-7 treatment reduced body weight, upregulated thermogenesis, and ameliorated impaired glucose homeostasis without affecting food consumption. Furthermore, Ang 1-7 treatment enlarged BAT and the increased expression of UCP1, PRDM16, and prohibitin. Alterations in PRDM16 expression correlated with increased AMPK and phosphorylation of mTOR. Ang 1-7 treatment elevated thermogenesis in subcutaneous white adipose tissue without altering UCP1 expression. These changes occurred in the context of decreased lipid accumulation in BAT from HFD-fed mice, preserved insulin signaling concomitant with phosphorylation of hormone-sensitive lipase and decreased expression of perilipin. These data suggest that Ang 1-7 induces brown adipocyte differentiation leading to upregulation of thermogenesis and improved metabolic profile in diet-induced obesity. Enhancing Ang 1-7 action represents a promising therapy to increase BAT and to reduce the metabolic complications associated with diet-induced obesity.