Is REDD1 a Metabolic Éminence Grise?
Is REDD1 a Metabolic Éminence Grise?
复制标题
DOI：
10.1016/j.tem.2016.08.005
复制
发表时间：
2016-12
影响因子：
10.9
通讯作者：
Hundal, Harinder S.
中科院分区：
文献类型：
--
作者：
Lipina, Christopher;Hundal, Harinder S.
调控发育和DNA损伤反应1(Redd1)在功能上与多种细胞过程的控制有关，至少部分是因为它能够抑制哺乳动物或机械雷帕霉素靶标(MTOR)复合体-1(MTORC1)，这是一个受激素和营养信号控制的关键蛋白质复合体。值得注意的是，新出现的证据表明，Redd1还调节着几条参与调节能量平衡和新陈代谢的途径。在这里，我们讨论了Redd1作为胰岛素作用和代谢功能的关键调节因子的证据，包括它对线粒体生物学和胰岛功能的潜在贡献。总而言之，现有证据表明，Redd1在能量平衡中的作用比之前认为的更突出，并暗示Redd1可能成为治疗代谢紊乱的治疗靶点。Redd1参与了一系列细胞过程，至少部分是由于其与影响蛋白质稳态和代谢功能的蛋白质相互作用的能力。一些肥胖相关因素，包括高胰岛素血症、高脂血症和低氧，已被证明上调Redd1，这可能通过受损的PKB/Akt信号转导促进胰岛素抵抗的发展。据报道，Redd1的基因抑制通过mTORC1/S6K通路的失调而削弱胰岛素敏感性。新出现的证据表明，Redd1是线粒体氧化能力和脂肪生成的关键调节者，也是调节胰岛素产生和分泌的关键因素。了解Redd1在胰岛素作用和能量平衡中的作用，可能为设计对抗肥胖相关代谢紊乱的策略提供路线图。
Regulated in development and DNA damage response 1 (REDD1) has been functionally linked to the control of diverse cellular processes due, at least in part, to its ability to repress mammalian or mechanistic Target of Rapamycin (mTOR) Complex-1 (mTORC1), a key protein complex controlled by hormonal and nutrient cues. Notably, emerging evidence suggests that REDD1 also regulates several pathways involved in modulating energy balance and metabolism. Herein, we discuss evidence implicating REDD1 as a key modulator of insulin action and metabolic function, including its potential contribution to mitochondrial biology and pancreatic islet function. Collectively, the available evidence suggests that REDD1 has a more prominent role in energy homeostasis than was previously thought, and implicates REDD1 as a potential therapeutic target for treatment of metabolic disorders. REDD1 has been implicated in a range of cellular processes due, at least in part, to its ability to interact with proteins that impact protein homeostasis and metabolic function Several obesity-related factors, including hyperinsulinaemia, hyperlipidaemia, and hypoxia, have been shown to upregulate REDD1, which may facilitate the development of insulin resistance through impaired PKB/Akt-directed signalling. Genetic inhibition of REDD1 has been reported to impair insulin sensitivity through dysregulation of the mTORC1/S6K pathway. Emerging evidence suggests that REDD1 acts as a key regulator of mitochondrial oxidative capacity and lipogenesis, as well as modulating insulin production and secretion. Understanding the role of REDD1 in insulin action and energy homeostasis may provide a roadmap toward designing strategies to counteract obesity-related metabolic disorders.
登录
查看更多内容
影响因子：
1.9
作者：
Dungan, Cory M.;Li, Ji;Williamson, David L.
通讯作者：
Williamson, David L.
影响因子：
9.8
作者：
CHLOUVERAKIS, C;DADE, EF;BATT, RAL
通讯作者：
BATT, RAL
影响因子：
64.5
作者：
Demetriades C;Doumpas N;Teleman AA
通讯作者：
Teleman AA
影响因子：
64.8
作者：
Cunningham, John T.;Rodgers, Joseph T.;Puigserver, Pere
通讯作者：
Puigserver, Pere
影响因子：
3.5
作者：
Cross, DAE;Watt, PW;Cohen, P
通讯作者：
Cohen, P