Differences in the redox status of human visceral and subcutaneous adipose tissues - relationships to obesity and metabolic risk

Differences in the redox status of human visceral and subcutaneous adipose tissues - relationships to obesity and metabolic risk
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DOI:
10.1016/j.metabol.2014.01.009
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发表时间:
2014-05-01
影响因子:
9.8
通讯作者:
Korac, Bato
Korac, Bato
中科院分区:
医学1区
文献类型:
--
作者:
Jankovic, Aleksandra;Korac, Aleksandra;Korac, Bato

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目标。代谢动态平衡依赖于脂肪细胞的代谢反应/过程,其中大部分是氧化还原调节的。此外,内脏脂肪组织和皮下脂肪组织(分别为VAT和SAT)在代谢和对代谢并发症的贡献方面存在差异,但它们在人类中的氧化还原特性仍不清楚。为了了解代谢综合征发生的分子机制,我们分析了不同体重和代谢风险组的VAT和SAT的氧化还原特性。材料和方法。根据体重指数将50名绝经前妇女分为正常体重组和肥胖组,并根据胰岛素抵抗(HOMA-IR)指数和甘油三酯、总胆固醇、低密度脂蛋白和高密度脂蛋白水平的稳态模型评估将这些组进一步细分为代谢健康组和代谢性肥胖(风险组)。分析VAT和SAT的抗氧化组分、NADPH氧化酶蛋白和4-羟基壬烯醛(4-HNE)水平。与SAT相比,VAT显示出更高的谷胱甘肽(GSH)基础水平和GSH依赖酶活性。与代谢健康的正常体重对照组相比,肥胖女性组在两个储存库中都显示出较低的GSH水平。然而,在这些组中,仅在VAT中观察到了额外的前氧化改变(NADPH氧化酶和4-HNE升高,SOD和/或CAT水平下降)。由于硫醇-氧化还原动态平衡在脂肪生成中的关键作用,依赖于GSH的抗氧化剂部分的库间差异可能与VAT中发现的更高的代谢活性有关。类似地,肥胖期间出现的较低GSH水平和相应的额外氧化还原失衡可能是VAT代谢功能障碍的迹象,而VAT代谢功能障碍是随后的代谢损伤的基础。(C)2014 Elsevier Inc.保留所有权利。
Objective. Metabolic homeostasis depends on adipocyte metabolic responses/processes, most of which are redox-regulated. Besides, visceral and subcutaneous adipose tissues (VAT and SAT, respectively) differ metabolically and in their contribution to metabolic complications, but their redox characteristics in humans are still unknown. To understand the molecular mechanisms of metabolic syndrome development, we analysed the redox characteristics of VAT and SAT in groups with various body weights and metabolic risks.Material and Methods. Fifty premenopausal women were classified according to body mass index into normal-weight and obese groups, and these groups were further sub-classified into metabolically healthy and metabolically obese ("at risk") based on the homeostasis model assessment of insulin resistance (HOMA-IR) index and the triglyceride, total-, LDL- and HDL-cholesterol levels. Antioxidant components, NADPH oxidase protein and 4-hydroxynonenal (4-HNE) levels were analysed in VAT and SAT.Results. Compared with the SAT, the VAT showed a higher basal level of glutathione (GSH) and GSH-dependent enzyme activities. Compared with the metabolically healthy normal-weight controls, the obese groups of women showed lower GSH levels in both depots. However, in these groups, additional prooxidative changes (increased NADPH oxidase and 4-HNE and decreased levels of SOD and/or CAT) were observed only in VAT.Conclusions. Because of the critical role of thiol-redox homeostasis in lipogenesis, interdepot-differences in the GSH-dependent antioxidant part may be connected to the higher metabolic activity found in VAT. Analogously, the lower GSH levels that occur during obesity and the corresponding additional redox imbalance may be signs of VAT metabolic dysfunction that underlie the subsequent metabolic impairment. (C) 2014 Elsevier Inc. All rights reserved.