Wei Hong-Kui, Deng Zhao, Jiang Shu-Zhong, Song Tong-Xing, Zhou Yuan-Fei, Peng Jian, Tao Ya-Xiong
Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, 430070, Wuhan, PR China.
Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, 430070, Wuhan, PR China.
Mol Cell Endocrinol. 2017 Jan 5;439:116-125. doi: 10.1016/j.mce.2016.10.029. Epub 2016 Oct 28.
Dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) increase insulin signaling in skeletal muscle. In the current study, we investigated the effect of eicosapentaenoic acid (EPA) on insulin-induced mammalian target of rapamycin (mTOR) phosphorylation in myotubes. We showed that EPA did not affect basal and insulin-induced mTOR phosphorylation in myotubes. However, EPA abolished lipopolysaccharide (LPS) -induced deficiency in insulin signaling (P < 0.05). Pre-incubation of nuclear factor κB (NF-κΒ) and c-Jun N-terminal kinases (JNK) inhibitors prevented the decreased insulin-induced mTOR phosphorylation elicited by LPS (P < 0.05). In addition, in protein tyrosine phosphatase-1B (PTP1B) knockdown myotubes, LPS failed to decrease insulin-induced mammalian target of rapamycin (mTOR) phosphorylation in myotubes (P > 0.05). In myotubes, LPS stimulated PTP1B expression via NF-κB and activation protein-1 (AP1). Pre-incubation of 50 μM EPA prevented the LPS-induced activation of AP1 and NF-κΒ as well as PTP1B expression (P < 0.05). Interestingly, incubation of peroxisome proliferator-activated receptor γ (PPARγ) antagonist (GW9662) prior to EPA treatment, the effect of EPA on insulin-induced mTOR phosphorylation was blocked. Accordingly, EPA did not inhibit the LPS-induced activation of AP1 or NF-κΒ as well as PTP1B expression when incubation of GW9662 prior to EPA treatment. The in vivo study showed that EPA prevented LPS-induced PTPT1B expression and a decrease in insulin-induced mTOR phosphorylation in muscle of mice. In summary, EPA abolished LPS inhibition of insulin-induced mTOR phosphorylation in myotubes, and one of the key mechanisms was to inhibit AP1 and NF-κB activation and PTP1B transcription.
膳食中的n-3多不饱和脂肪酸（n-3 PUFAs）可增强骨骼肌中的胰岛素信号传导。在本研究中，我们调查了二十碳五烯酸（EPA）对肌管中胰岛素诱导的哺乳动物雷帕霉素靶蛋白（mTOR）磷酸化的影响。我们发现，EPA不影响肌管中的基础mTOR磷酸化水平以及胰岛素诱导的mTOR磷酸化。然而，EPA消除了脂多糖（LPS）诱导的胰岛素信号传导缺陷（P < 0.05）。预先孵育核因子κB（NF-κΒ）和c-Jun氨基末端激酶（JNK）抑制剂可防止LPS引起的胰岛素诱导的mTOR磷酸化降低（P < 0.05）。此外，在蛋白酪氨酸磷酸酶-1B（PTP1B）敲低的肌管中，LPS未能降低肌管中胰岛素诱导的哺乳动物雷帕霉素靶蛋白（mTOR）磷酸化水平（P > 0.05）。在肌管中，LPS通过NF-κB和激活蛋白-1（AP1）刺激PTP1B表达。预先孵育50 μM EPA可防止LPS诱导的AP1和NF-κΒ激活以及PTP1B表达（P < 0.05）。有趣的是，在EPA处理前孵育过氧化物酶体增殖物激活受体γ（PPARγ）拮抗剂（GW9662），EPA对胰岛素诱导的mTOR磷酸化的作用被阻断。因此，在EPA处理前孵育GW9662时，EPA不会抑制LPS诱导的AP1或NF-κΒ激活以及PTP1B表达。体内研究表明，EPA可防止LPS诱导的小鼠肌肉中PTPT1B表达以及胰岛素诱导的mTOR磷酸化降低。总之, EPA消除了LPS对肌管中胰岛素诱导的mTOR磷酸化的抑制作用，其中一个关键机制是抑制AP1和NF-κB激活以及PTP1B转录。
