Xie Weisheng, Hamilton James A, Kirkland James L, Corkey Barbara E, Guo Wen
Obesity Research Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Lipids. 2006 Mar;41(3):267-71. doi: 10.1007/s11745-006-5096-4.
Exogenous FA cause lipid accumulation in pre-adipocytes. We investigated whether the fat cells thus formed are metabolically distinct from adipocytes differentiated with standard methylisobutylxanthine, dexamethasone, and insulin (MDI) hormonal cocktail by comparing their expression of adipogenic genes, accumulation of TAG, lipogenesis, lipolysis, glucose uptake, and the effects of insulin on selected metabolic activities. Cells exposed to oleate began to accumulate TAG in parallel or prior to the induction of adipogenic genes, whereas cells treated with MDI expressed adipogenic genes before TAG accumulation. Oleate-treated fat cells also showed exaggerated basal lipolysis and weak response to insulin in both lipolysis regulation and glucose uptake. These findings were associated with increased basal phosphorylation of perilipin, increased Glut-1 but decreased Glut-4 expression, and reduced insulin-induced Akt phosphorylation. We suggest that this unique fat cell phenotype might be a mimetic of what can happen to fat cells formed in vivo under the influence of circulating FA and might be a useful model for in vitro studies of obesity-related insulin resistance in adipocytes.
外源性脂肪酸导致前脂肪细胞中脂质积累。我们通过比较脂肪生成基因的表达、甘油三酯（TAG）的积累、脂肪生成、脂肪分解、葡萄糖摄取以及胰岛素对选定代谢活动的影响，研究了由此形成的脂肪细胞在代谢上是否与用标准甲基异丁基黄嘌呤、地塞米松和胰岛素（MDI）激素混合物分化的脂肪细胞不同。暴露于油酸的细胞在脂肪生成基因诱导之前或同时开始积累TAG，而用MDI处理的细胞在TAG积累之前表达脂肪生成基因。油酸处理的脂肪细胞在基础脂肪分解方面也表现出增强，并且在脂肪分解调节和葡萄糖摄取方面对胰岛素的反应较弱。这些发现与围脂滴蛋白的基础磷酸化增加、葡萄糖转运蛋白-1（Glut-1）表达增加但葡萄糖转运蛋白-4（Glut-4）表达降低以及胰岛素诱导的蛋白激酶B（Akt）磷酸化减少有关。我们认为，这种独特的脂肪细胞表型可能模拟了在循环脂肪酸影响下体内形成的脂肪细胞可能发生的情况，并且可能是用于体外研究脂肪细胞中与肥胖相关的胰岛素抵抗的有用模型。
