人体白色脂肪组织在肥胖状态下表现出选择性胰岛素抵抗。
Human White Adipose Tissue Displays Selective Insulin Resistance in the Obese State.
机构信息
Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
Department of Medicine (H7), Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
出版信息
Diabetes. 2021 Jul;70(7):1486-1497. doi: 10.2337/db21-0001. Epub 2021 Apr 16.
Selective hepatic insulin resistance is a feature of obesity and type 2 diabetes. Whether similar mechanisms operate in white adipose tissue (WAT) of those with obesity and to what extent these are normalized by weight loss are unknown. We determined insulin sensitivity by hyperinsulinemic euglycemic clamp and insulin response in subcutaneous WAT by RNA sequencing in 23 women with obesity before and 2 years after bariatric surgery. To control for effects of surgery, women postsurgery were matched to never-obese women. Multidimensional analyses of 138 samples allowed us to classify the effects of insulin into three distinct expression responses: a common set was present in all three groups and included genes encoding several lipid/cholesterol biosynthesis enzymes; a set of obesity-attenuated genes linked to tissue remodeling and protein translation was selectively regulated in the two nonobese states; and several postobesity-enriched genes encoding proteins involved in, for example, one-carbon metabolism were only responsive to insulin in the women who had lost weight. Altogether, human WAT displays a selective insulin response in the obese state, where most genes are normalized by weight loss. This comprehensive atlas provides insights into the transcriptional effects of insulin in WAT and may identify targets to improve insulin action.
选择性肝胰岛素抵抗是肥胖和 2 型糖尿病的特征。在肥胖人群的白色脂肪组织(WAT)中是否存在类似的机制,以及这些机制在多大程度上可以通过减肥来正常化尚不清楚。我们通过对 23 名肥胖女性在接受减肥手术前和手术后 2 年进行超胰岛素正葡萄糖钳夹和皮下 WAT 的 RNA 测序,确定了胰岛素敏感性和胰岛素反应。为了控制手术的影响,手术后的女性与从未肥胖过的女性相匹配。对 138 个样本的多维分析使我们能够将胰岛素的作用分类为三种不同的表达反应:一组常见的基因存在于所有三组中,包括编码几种脂质/胆固醇生物合成酶的基因;一组与组织重塑和蛋白质翻译相关的肥胖减弱基因选择性地在两种非肥胖状态下受到调节;而一些肥胖后富集的基因编码涉及例如一碳代谢的蛋白质,仅在减肥的女性中对胰岛素有反应。总的来说,人类 WAT 在肥胖状态下表现出选择性的胰岛素反应,大多数基因通过减肥而得到正常化。这个全面的图谱提供了对 WAT 中胰岛素转录效应的深入了解,并可能确定改善胰岛素作用的靶点。