Wentworth J M, Naselli G, Ngui K, Smyth G K, Liu R, O'Brien P E, Bruce C, Weir J, Cinel M, Meikle P J, Harrison L C
Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Monash University Centre for Obesity Research and Education, Melbourne, Victoria, Australia.
Int J Obes (Lond). 2016 Apr;40(4):706-13. doi: 10.1038/ijo.2015.223. Epub 2015 Oct 26.
The association between central obesity and insulin resistance reflects the properties of visceral adipose tissue. Our aim was to gain further insight into this association by analysing the lipid composition of subcutaneous and omental adipose tissue in obese women with and without insulin resistance.
Subcutaneous and omental adipose tissue and serum were obtained from 29 obese non-diabetic women, 13 of whom were hyperinsulinemic. Histology, lipid and gene profiling were performed.
In omental adipose tissue of obese, insulin-resistant women, adipocyte hypertrophy and macrophage infiltration were accompanied by an increase in GM3 ganglioside and its synthesis enzyme ST3GAL5; in addition, phosphatidylethanolamine (PE) lipids were increased and their degradation enzyme, phosphatidylethanolamine methyl transferase (PEMT), decreased. ST3GAL5 was expressed predominantly in adipose stromovascular cells and PEMT in adipocytes. Insulin resistance was also associated with an increase in PE lipids in serum.
The relevance of these findings to insulin resistance in humans is supported by published mouse studies, in which adipocyte GM3 ganglioside, increased by the inflammatory cytokine tumour necrosis factor-α, impaired insulin action and PEMT was required for adipocyte lipid storage. Thus in visceral adipose tissue of obese humans, an increase in GM3 ganglioside secondary to inflammation may contribute to insulin resistance and a decrease in PEMT may be a compensatory response to adipocyte hypertrophy.
中心性肥胖与胰岛素抵抗之间的关联反映了内脏脂肪组织的特性。我们的目的是通过分析有或无胰岛素抵抗的肥胖女性皮下和网膜脂肪组织的脂质组成，进一步深入了解这种关联。
从29名肥胖非糖尿病女性中获取皮下和网膜脂肪组织及血清，其中13名女性存在高胰岛素血症。进行了组织学、脂质和基因分析。
在肥胖且有胰岛素抵抗的女性的网膜脂肪组织中，脂肪细胞肥大和巨噬细胞浸润伴随着GM3神经节苷脂及其合成酶ST3GAL5的增加；此外，磷脂酰乙醇胺（PE）脂质增加，其降解酶磷脂酰乙醇胺甲基转移酶（PEMT）减少。ST3GAL5主要在脂肪血管基质细胞中表达，而PEMT在脂肪细胞中表达。胰岛素抵抗还与血清中PE脂质的增加有关。
已发表的小鼠研究支持了这些发现与人类胰岛素抵抗的相关性，在这些研究中，炎症细胞因子肿瘤坏死因子-α导致脂肪细胞GM3神经节苷脂增加，损害胰岛素作用，而PEMT是脂肪细胞脂质储存所必需的。因此，在肥胖人类的内脏脂肪组织中，炎症继发的GM3神经节苷脂增加可能导致胰岛素抵抗，而PEMT减少可能是对脂肪细胞肥大的一种代偿反应。
