Department of Child Health, Huai'an Maternity and Child Health Hospital, Huai'an 223002, China.
J Bioenerg Biomembr. 2012 Jun;44(3):357-63. doi: 10.1007/s10863-012-9440-5. Epub 2012 Apr 21.
NYGGF4 (also called PID1) was demonstrated that it may be related to the development of obesity-related IR. We aimed in the present study to further elucidate the effects of NYGGF4 on IR and the underlying mechanisms through using α-Lipoic acid (LA) treatment, which could facilitate glucose transport and utilization in fully differentiated adipocytes. Our data showed that the LA pretreatment strikingly enhanced insulin-stimulated glucose uptake through increasing GLUT4 translocation to the PM in NYGGF4 overexpression adipocytes. The reactive oxygen species (ROS) levels in NYGGF4 overexpression adipocytes were strikingly enhanced, which could be decreased by the LA pretreatment. NYGGF4 overexpression resulted in significant inhibition of tyrosine phosphorylation of IRS-1 and serine phosphorylation of Akt, whereas incubation with LA strongly activated IRS-1 and Akt phosphorylation in NYGGF4 overexpression adipocytes. These results suggest that LA protects 3T3-L1 adipocytes from NYGGF4-induced IR partially through increasing phosphorylation of IRS-1 and Akt and provide evidence that NYGGF4 may be a potential target for the treatment of obesity and obesity-related IR.
NYGGF4（也称为 PID1）被证明可能与肥胖相关的 IR 的发展有关。我们旨在本研究中通过使用α-硫辛酸（LA）治疗，进一步阐明 NYGGF4 对 IR 的影响及其潜在机制，α-硫辛酸可以促进完全分化的脂肪细胞中的葡萄糖转运和利用。我们的数据表明，LA 预处理可通过增加 NYGGF4 过表达脂肪细胞中 GLUT4 向 PM 的易位，显著增强胰岛素刺激的葡萄糖摄取。NYGGF4 过表达脂肪细胞中的活性氧（ROS）水平显著增强，而 LA 预处理可降低其水平。NYGGF4 过表达导致 IRS-1 的酪氨酸磷酸化和 Akt 的丝氨酸磷酸化显著抑制，而 LA 孵育可强烈激活 NYGGF4 过表达脂肪细胞中 IRS-1 和 Akt 的磷酸化。这些结果表明，LA 通过增加 IRS-1 和 Akt 的磷酸化，部分保护 3T3-L1 脂肪细胞免受 NYGGF4 诱导的 IR，并为 NYGGF4 可能成为肥胖和肥胖相关 IR 治疗的潜在靶点提供证据。
