Department of Food and Nutrition, Seoul National University, Seoul, Korea.
Metabolism. 2010 Jul;59(7):927-34. doi: 10.1016/j.metabol.2009.10.012. Epub 2009 Dec 16.
Previous studies showed that increased release of free fatty acids from adipocytes leads to insulin resistance and triglyceride (TG) accumulation in the liver, which may progress into hepatic steatohepatitis. We and other investigators have previously reported that palmitate induces endoplasmic reticulum stress-mediated toxicity in several tissues. This work investigated whether palmitate could induce insulin resistance and steatosis in HepG2 cells. We treated cells with either saturated fatty acid (palmitate) or unsaturated fatty acid (oleate), and observed that palmitate significantly activated c-jun N-terminal kinase and inactivated protein kinase B. Both 4-phenylbutyric acid and glycerol significantly activated protein kinase B, confirming the involvement of endoplasmic reticulum stress in palmitate-mediated insulin resistance. Oleate, but not palmitate, significantly induced intracellular TG deposition and activated sterol regulatory element binding protein-1. Instead, diacylglycerol level and protein kinase C epsilon activity were significantly increased by palmitate, suggesting the possible role of diacylglycerol in palmitate-mediated lipotoxicity. Therefore, the present study clearly showed that palmitate impairs insulin resistance, but does not induce significant TG accumulation in HepG2 cells.
先前的研究表明，脂肪细胞中游离脂肪酸的释放增加会导致胰岛素抵抗和肝脏甘油三酯（TG）积累，这可能进一步发展为肝脂肪性肝炎。我们和其他研究人员之前曾报道过，棕榈酸可诱导多种组织中的内质网应激介导的毒性。本研究旨在探讨棕榈酸是否可诱导 HepG2 细胞发生胰岛素抵抗和脂肪变性。我们用饱和脂肪酸（棕榈酸）或不饱和脂肪酸（油酸）处理细胞，结果发现棕榈酸可显著激活 c-jun N 端激酶并使蛋白激酶 B 失活。4-苯基丁酸和甘油均可显著激活蛋白激酶 B，证实了内质网应激参与了棕榈酸介导的胰岛素抵抗。油酸可显著诱导细胞内 TG 沉积并激活固醇调节元件结合蛋白-1，但棕榈酸却不能。相反，二酰基甘油水平和蛋白激酶 C ε 活性显著增加，提示二酰基甘油可能在棕榈酸介导的脂毒性中发挥作用。因此，本研究清楚地表明，棕榈酸可损害胰岛素抵抗，但不会在 HepG2 细胞中诱导明显的 TG 积累。
