Cardiac natriuretic peptides promote adipose 'browning' through mTOR complex-1.
Cardiac natriuretic peptides promote adipose 'browning' through mTOR complex-1.
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心脏利钠肽通过mTOR复合物-1促进脂肪“布朗宁”。
DOI：
10.1016/j.molmet.2017.12.017
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发表时间：
2018-03
影响因子：
8.1
通讯作者：
Collins S
中科院分区：
文献类型：
--
作者：
Liu D;Ceddia RP;Collins S
棕色脂肪组织 (BAT) 中生热作用的激活以及增加白色脂肪中解偶联蛋白 1 (UCP1) 水平和线粒体生物合成（称为“褐变”）的能力，由于能量消耗的净增加，对于治疗肥胖及其合并症具有巨大的治疗潜力。长期以来人们都知道β-肾上腺素能-cAMP-PKA 信号传导可以调节这些过程。最近，哺乳动物雷帕霉素靶点复合物 1 (mTORC1) 的 PKA 依赖性激活被证明对于脂肪“褐变”以及肩胛间 BAT 的正常发育是必要的。除了 cAMP-PKA 信号通路外，cGMP-PKG 信号通路也促进这种褐变过程。然而，尚不清楚 mTORC1 是否也是 cGMP-PKG 诱导褐变所必需的。利尿钠肽 (NP) 结合并激活膜结合鸟苷酸环化酶 NP 受体 A (NPRA)，对 mTORC1 的激活进行了体外小鼠和人类脂肪细胞以及小鼠体内脂肪组织的评估。在小鼠和人类脂肪细胞中均观察到 NP-cGMP 信号传导激活 mTORC1。我们发现，NP-NPRA-PKG 信号通过直接 PKG 磷酸化 Raptor 的丝氨酸 791 来激活 mTORC1。给小鼠施用 B 型利尿钠肽 (BNP) 会诱导体内腹股沟脂肪组织中 Ucp1 的表达，但这种表达被 mTORC1 抑制剂雷帕霉素完全阻断。我们的结果表明，NP-cGMP 信号通过 PKG 激活 mTORC1，这是脂肪褐变机制的一个组成部分。利钠肽-cGMP 信号传导在体外激活脂肪细胞中的 mTORC1。利钠肽-cGMP 信号传导可激活体内脂肪组织中的 mTORC1。利钠肽信号传导刺激 Raptor 磷酸化。 mTORC1 对于体内 BNP 引起的腹股沟白色脂肪组织褐变是必需的。
Activation of thermogenesis in brown adipose tissue (BAT) and the ability to increase uncoupling protein 1 (UCP1) levels and mitochondrial biogenesis in white fat (termed ‘browning’), has great therapeutic potential to treat obesity and its comorbidities because of the net increase in energy expenditure. β-adrenergic-cAMP-PKA signaling has long been known to regulate these processes. Recently PKA-dependent activation of mammalian target of rapamycin complex 1 (mTORC1) was shown to be necessary for adipose ‘browning’ as well as proper development of the interscapular BAT. In addition to cAMP-PKA signaling pathways, cGMP-PKG signaling also promotes this browning process; however, it is unclear whether or not mTORC1 is also necessary for cGMP-PKG induced browning. Activation of mTORC1 by natriuretic peptides (NP), which bind to and activate the membrane-bound guanylyl cyclase, NP receptor A (NPRA), was assessed in mouse and human adipocytes in vitro and mouse adipose tissue in vivo. Activation of mTORC1 by NP-cGMP signaling was observed in both mouse and human adipocytes. We show that NP-NPRA-PKG signaling activate mTORC1 by direct PKG phosphorylation of Raptor at Serine 791. Administration of B-type natriuretic peptide (BNP) to mice induced Ucp1 expression in inguinal adipose tissue in vivo, which was completely blocked by the mTORC1 inhibitor rapamycin. Our results demonstrate that NP-cGMP signaling activates mTORC1 via PKG, which is a component in the mechanism of adipose browning. Natriuretic peptide-cGMP signaling activates mTORC1 in adipocytes in vitro. Natriuretic peptide-cGMP signaling activates mTORC1 in adipose tissue in vivo. Natriuretic peptides signaling stimulates Raptor phosphorylation. mTORC1 is necessary for BNP-evoked browning of inguinal white adipose tissue in vivo.
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DOI：
10.1016/j.tem.2017.01.004
发表时间：
2017-05
期刊：
Trends in endocrinology and metabolism: TEM
影响因子：
--
作者：
Lee PL;Jung SM;Guertin DA
通讯作者：
Guertin DA
影响因子：
20.1
作者：
Sansbury BE;Cummins TD;Tang Y;Hellmann J;Holden CR;Harbeson MA;Chen Y;Patel RP;Spite M;Bhatnagar A;Hill BG
通讯作者：
Hill BG
影响因子：
7.3
作者：
Nisoli, E;Clementi, E;Carruba, MO
通讯作者：
Carruba, MO
影响因子：
4.8
作者：
Scott, PH;Lawrence, JC
通讯作者：
Lawrence, JC
DOI：
10.1165/rcmb.2012-0043oc
发表时间：
2013-01-01
影响因子：
6.4
作者：
Park, Hyoung-Sook;Park, Jong-Wan;Chun, Yang-Sook
通讯作者：
Chun, Yang-Sook