Increased adipocyte O2 consumption triggers HIF-1α, causing inflammation and insulin resistance in obesity.
Increased adipocyte O2 consumption triggers HIF-1α, causing inflammation and insulin resistance in obesity.
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DOI：
10.1016/j.cell.2014.05.012
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发表时间：
2014-06-05
期刊：
影响因子：
64.5
通讯作者：
Olefsky JM
中科院分区：
文献类型：
--
作者：
Lee YS;Kim JW;Osborne O;Oh DY;Sasik R;Schenk S;Chen A;Chung H;Murphy A;Watkins SM;Quehenberger O;Johnson RS;Olefsky JM
脂肪组织缺氧和炎症已被认为与肥胖引起的胰岛素抵抗有关。在这里，我们报告了在高脂饮食(HFD)喂养和肥胖的早期过程中，脂肪细胞的呼吸变得不耦合，导致氧耗增加和脂肪细胞相对缺氧的状态。这些事件足以触发HIF-1α的诱导，引发肥胖所特有的慢性脂肪组织炎症反应。在分子水平上，这些事件涉及饱和脂肪酸对腺嘌呤核苷酸转位酶2(ANT2)的刺激，ANT2是线粒体膜内的一种蛋白质，导致非偶联呼吸状态。基因或药物抑制ANT2或HIF-1α可以预防或逆转这些病理生理事件，恢复胰岛素敏感性和糖耐量状态。这些结果揭示了肥胖引起的炎症和胰岛素抵抗的一系列事件。
Adipose tissue hypoxia and inflammation has been causally implicated in obesity-induced insulin resistance. Here we report that early in the course of high fat diet (HFD) feeding and obesity, adipocyte respiration becomes uncoupled, leading to increased oxygen consumption and a state of relative adipocyte hypoxia. These events are sufficient to trigger HIF-1α induction, setting off the chronic adipose tissue inflammatory response characteristic of obesity. At the molecular level, these events involve saturated fatty acid stimulation of the adenine nucleotide translocase 2 (ANT2), an inner mitochondrial membrane protein, which leads to the uncoupled respiratory state. Genetic or pharmacologic inhibition of either ANT2 or HIF-1α can prevent or reverse these pathophysiologic events, restoring a state of insulin sensitivity and glucose tolerance. These results reveal the sequential series of events in obesity-induced inflammation and insulin resistance.
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影响因子：
29
作者：
Lee KY;Gesta S;Boucher J;Wang XL;Kahn CR
通讯作者：
Kahn CR
影响因子：
29
作者：
Chalkiadaki A;Guarente L
通讯作者：
Guarente L
影响因子：
29
作者：
Deng T;Lyon CJ;Minze LJ;Lin J;Zou J;Liu JZ;Ren Y;Yin Z;Hamilton DJ;Reardon PR;Sherman V;Wang HY;Phillips KJ;Webb P;Wong ST;Wang RF;Hsueh WA
通讯作者：
Hsueh WA
影响因子：
7.7
作者：
Lee YS;Li P;Huh JY;Hwang IJ;Lu M;Kim JI;Ham M;Talukdar S;Chen A;Lu WJ;Bandyopadhyay GK;Schwendener R;Olefsky J;Kim JB
通讯作者：
Kim JB
DOI：
10.1073/pnas.2536828100
发表时间：
2003-12-23
影响因子：
11.1
作者：
He, WM;Barak, Y;Evans, RM
通讯作者：
Evans, RM