GPS2 Deficiency Triggers Maladaptive White Adipose Tissue Expansion in Obesity via HIF1A Activation.
GPS2 Deficiency Triggers Maladaptive White Adipose Tissue Expansion in Obesity via HIF1A Activation.
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DOI：
10.1016/j.celrep.2018.08.032
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发表时间：
2018-09-11
期刊：
影响因子：
8.8
通讯作者：
Venteclef N
中科院分区：
文献类型：
--
作者：
Drareni K;Ballaire R;Barilla S;Mathew MJ;Toubal A;Fan R;Liang N;Chollet C;Huang Z;Kondili M;Foufelle F;Soprani A;Roussel R;Gautier JF;Alzaid F;Treuter E;Venteclef N
肥厚的白色脂肪组织（WAT）代表了一种与人类发展为2型糖尿病风险相关的不适应机制。然而，使WAT倾向于肥大的分子事件尚未明确。在这里，我们证明脂肪细胞肥大是由肥胖过程中协同抑制因子GPS2的缺失引发的。小鼠脂肪细胞特异性GPS2缺乏症（GPS2 AKO）在能量过剩时导致脂肪细胞肥大、炎症和线粒体功能障碍。这种表型是由HIF1A激活驱动的，HIF1A激活协调了WAT重塑不足并破坏了线粒体活性，这可以通过药物或遗传HIF1A抑制来逆转。人类脂肪组织中基因表达的相关分析显示GPS2与HIF1A、脂肪细胞肥大和胰岛素抵抗呈负相关。因此，我们提出肥胖相关的脂肪细胞中GPS2的缺失易导致小鼠和人类的WAT扩张和糖尿病前期状态。脂肪特异性GPS2缺乏易导致脂肪细胞肥大GPS2缺失会触发HIF1A通路的转录激活GPS2-HIF1A相互作用的解除会引起线粒体活性的破坏，在人类脂肪组织中GPS2和HIF1A水平呈负相关，Drareni等人发现了转录辅助抑制因子GPS2在脂肪细胞肥大的调节中的作用。他们提供的证据表明，脂肪细胞特异性GPS2的缺失通过激活HIF1A转录活性，易导致脂肪组织的不适应扩张和糖尿病前期状态。
Hypertrophic white adipose tissue (WAT) represents a maladaptive mechanism linked to the risk for developing type 2 diabetes in humans. However, the molecular events that predispose WAT to hypertrophy are poorly defined. Here, we demonstrate that adipocyte hypertrophy is triggered by loss of the corepressor GPS2 during obesity. Adipocyte-specific GPS2 deficiency in mice (GPS2 AKO) causes adipocyte hypertrophy, inflammation, and mitochondrial dysfunction during surplus energy. This phenotype is driven by HIF1A activation that orchestrates inadequate WAT remodeling and disrupts mitochondrial activity, which can be reversed by pharmacological or genetic HIF1A inhibition. Correlation analysis of gene expression in human adipose tissue reveals a negative relationship between GPS2 and HIF1A, adipocyte hypertrophy, and insulin resistance. We propose therefore that the obesity-associated loss of GPS2 in adipocytes predisposes for a maladaptive WAT expansion and a pro-diabetic status in mice and humans. Adipose-specific GPS2 deficiency predisposes for adipocyte hypertrophy Loss of GPS2 triggers transcriptional activation of HIF1A pathways Deregulation of GPS2-HIF1A interplay provokes disrupted mitochondrial activity GPS2 and HIF1A levels are negatively correlated in human adipose tissue Drareni et al. identify a role for the transcriptional corepressor GPS2 in the regulation of adipocyte hypertrophy. They provide evidence that adipocyte-specific loss of GPS2 predisposes toward maladaptive adipose tissue expansion and pro-diabetic status through activation of HIF1A transcriptional activity.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
影响因子：
16
作者：
Cardamone, M. Dafne;Krones, Anna;Tanasa, Bogdan;Taylor, Havilah;Ricci, Laura;Ohgi, Kenneth A.;Glass, Christopher K.;Rosenfeld, Michael G.;Perissi, Valentina
通讯作者：
Perissi, Valentina
影响因子：
8.1
作者：
Cederquist CT;Lentucci C;Martinez-Calejman C;Hayashi V;Orofino J;Guertin D;Fried SK;Lee MJ;Cardamone MD;Perissi V
通讯作者：
Perissi V
影响因子：
8.2
作者：
Choo, HJ;Kim, JH;Ko, YG
通讯作者：
Ko, YG