Role of adipocyte mitochondria in inflammation, lipemia and insulin sensitivity in humans: effects of pioglitazone treatment.
Role of adipocyte mitochondria in inflammation, lipemia and insulin sensitivity in humans: effects of pioglitazone treatment.
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DOI：
10.1038/ijo.2017.192
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发表时间：
2017-08-14
期刊：
影响因子：
--
通讯作者：
Meyer C
中科院分区：
文献类型：
--
作者：
Xie X;Sinha S;Yi Z;Langlais PR;Madan M;Bowen BP;Willis W;Meyer C
为了进一步了解脂肪细胞线粒体在人体全身脂质代谢、炎症和胰岛素敏感性中的作用，并更好地了解过氧化物酶体增殖体激活受体γ激动剂吡格列酮的作用机制。线粒体DNA拷贝数(mtDNA),线粒体分布、线粒体和整体细胞蛋白质丰度以及内在皮下脂肪细胞的线粒体功能进行评估,实时定量PCR, MitoTracker染色,全球蛋白质组学分析和NADH在胰岛素敏感细胞色素c还原酶活动,normal-glucose-tolerant (NGT)个人和年龄、性别、在吡格列酮治疗3个月前后，伴有糖耐量异常（AGT）的肥胖匹配胰岛素抵抗个体。AGT组mtDNA拷贝数/脂肪细胞和mtDNA拷贝数/脂肪细胞体积分别比NGT组低约55%和约4倍，与正糖钳m值和高密度脂蛋白呈正相关，与整个队列空腹血浆甘油三酯、肿瘤坏死因子-α和白细胞介素-6水平负相关。mtDNA拷贝数/脂肪细胞体积也与血浆脂联素呈正相关。吡格列酮改善了胰岛素敏感性、血脂和炎症，增加了线粒体拷贝数，导致线粒体从点状重新分布到更网状的模式，这在NGT中观察到。这与线粒体蛋白的丰度不成比例地增加有关，包括那些参与脂肪氧化和甘油三酯合成的蛋白。吡格列酮还增加了胶原VI的丰度，降低了细胞骨架蛋白的丰度。AGT组和NGT组离体脂肪细胞线粒体NADH细胞色素c还原酶活性相似，吡格列酮未改变其活性。脂肪细胞线粒体在胰岛素抵抗个体中缺乏，与全身脂质代谢、炎症和胰岛素敏感性相关。吡格列酮诱导线粒体的生物发生和重组，以及线粒体蛋白质的合成，包括那些对脂质代谢至关重要的蛋白质。它也改变细胞外基质和细胞骨架蛋白。脂肪细胞线粒体的内在功能似乎不受胰岛素抵抗和吡格列酮的影响。
To gain further insight into the role of adipocyte mitochondria in systemic lipid metabolism, inflammation and insulin sensitivity in humans and to provide a better understanding of the mechanisms of action of the peroxisome proliferator-activated receptor gamma agonist pioglitazone. Mitochondrial DNA (mtDNA) copy number, mitochondrial distribution, mitochondrial and overall cellular protein abundances as well as intrinsic mitochondrial function of subcutaneous adipocytes were assessed by real-time quantitative PCR, MitoTracker staining, global proteomics analyses and NADH cytochrome c reductase activity in insulin-sensitive, normal-glucose-tolerant (NGT) individuals and age, gender, adiposity-matched insulin-resistant individuals with abnormal glucose tolerant (AGT) before and after 3 months of pioglitazone treatment. mtDNA copy number/adipocyte and mtDNA copy number/adipocyte volume were ~ 55% and ~ 4-fold lower in AGT than in NGT, respectively, and correlated positively with the M-value of euglycemic clamps and high-density lipoprotein, and negatively with fasting plasma triglyceride, tumor necrosis factor-α and interleukin-6 levels in the entire cohort. mtDNA copy number/adipocyte volume also correlated positively with plasma adiponectin. Pioglitazone, which improved insulin sensitivity, plasma lipids and inflammation, increased the mitochondrial copy number, and led to a redistribution of mitochondria from a punctate to a more reticular pattern as observed in NGT. This was accompanied by disproportionately increased abundances of mitochondrial proteins, including those involved in fat oxidation and triglyceride synthesis. Pioglitazone also increased the abundance of collagen VI and decreased the abundance of cytoskeletal proteins. NADH cytochrome c reductase activity of isolated adipocyte mitochondria was similar in AGT and NGT and unaltered by pioglitazone. Adipocyte mitochondria are deficient in insulin-resistant individuals and correlate with systemic lipid metabolism, inflammation and insulin sensitivity. Pioglitazone induces mitochondrial biogenesis and reorganization as well as the synthesis of mitochondrial proteins including those critical for lipid metabolism. It also alters extracellular matrix and cytoskeletal proteins. The intrinsic function of adipocyte mitochondria appears unaffected in insulin resistance and by pioglitazone.
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影响因子：
8.2
作者：
Choo, HJ;Kim, JH;Ko, YG
通讯作者：
Ko, YG
影响因子：
5.8
作者：
Bogacka, I;Ukropcova, B;Smith, SR
通讯作者：
Smith, SR
影响因子：
10.9
作者：
Kusminski, Christine M.;Scherer, Philipp E.
通讯作者：
Scherer, Philipp E.
DOI：
10.1007/s13361-010-0051-2
发表时间：
2011-03
影响因子：
3.2
作者：
Geetha, Thangiah;Langlais, Paul;Luo, Moulun;Mapes, Rebekka;Lefort, Natalie;Chen, Shu-Chuan;Mandarino, Lawrence J.;Yi, Zhengping
通讯作者：
Yi, Zhengping
DOI：
10.1152/ajpcell.1996.270.2.c673
发表时间：
1996-02-01
影响因子：
5.5
作者：
Jackman, MR;Willis, WT
通讯作者：
Willis, WT