Park Jiyoung, Rho Ho Kyung, Kim Kang Ho, Choe Sung Sik, Lee Yun Sok, Kim Jae Bum
School of Biological Sciences, Seoul National University, San 56-1, Sillim-Dong, Kwanak-Gu, Seoul 151-742, South Korea.
Mol Cell Biol. 2005 Jun;25(12):5146-57. doi: 10.1128/MCB.25.12.5146-5157.2005.
Glucose-6-phosphate dehydrogenase (G6PD) produces cellular NADPH, which is required for the biosynthesis of fatty acids and cholesterol. Although G6PD is required for lipogenesis, it is poorly understood whether G6PD in adipocytes is involved in energy homeostasis, such as lipid and glucose metabolism. We report here that G6PD plays a role in adipogenesis and that its increase is tightly associated with the dysregulation of lipid metabolism and insulin resistance in obesity. We observed that the enzymatic activity and expression levels of G6PD were significantly elevated in white adipose tissues of obese models, including db/db, ob/ob, and diet-induced obesity mice. In 3T3-L1 cells, G6PD overexpression stimulated the expression of most adipocyte marker genes and elevated the levels of cellular free fatty acids, triglyceride, and FFA release. Consistently, G6PD knockdown via small interfering RNA attenuated adipocyte differentiation with less lipid droplet accumulation. Surprisingly, the expression of certain adipocytokines such as tumor necrosis factor alpha and resistin was increased, whereas that of adiponectin was decreased in G6PD overexpressed adipocytes. In accordance with these results, overexpression of G6PD impaired insulin signaling and suppressed insulin-dependent glucose uptake in adipocytes. Taken together, these data strongly suggest that aberrant increase of G6PD in obese and/or diabetic subjects would alter lipid metabolism and adipocytokine expression, thereby resulting in failure of lipid homeostasis and insulin resistance in adipocytes.
葡萄糖-6-磷酸脱氢酶（G6PD）产生细胞内的还原型辅酶II（NADPH），这是脂肪酸和胆固醇生物合成所必需的。尽管脂肪生成需要G6PD，但脂肪细胞中的G6PD是否参与能量稳态，如脂质和葡萄糖代谢，目前尚不清楚。我们在此报告，G6PD在脂肪生成中起作用，其增加与肥胖中脂质代谢失调和胰岛素抵抗密切相关。我们观察到，在肥胖模型（包括db/db、ob/ob和饮食诱导肥胖小鼠）的白色脂肪组织中，G6PD的酶活性和表达水平显著升高。在3T3-L1细胞中，G6PD过表达刺激了大多数脂肪细胞标记基因的表达，并提高了细胞游离脂肪酸、甘油三酯和游离脂肪酸释放水平。一致地，通过小干扰RNA敲低G6PD可减弱脂肪细胞分化，脂质小滴积累减少。令人惊讶的是，在G6PD过表达的脂肪细胞中，某些脂肪因子如肿瘤坏死因子α和抵抗素的表达增加，而脂联素的表达减少。与这些结果一致，G6PD过表达损害胰岛素信号传导并抑制脂肪细胞中胰岛素依赖性葡萄糖摄取。综上所述，这些数据强烈表明，肥胖和/或糖尿病患者中G6PD的异常增加会改变脂质代谢和脂肪因子表达，从而导致脂肪细胞脂质稳态失衡和胰岛素抵抗。
