Exercise improves lipid metabolism disorders induced by high-fat diet in a SESN2/JNK-independent manner
Exercise improves lipid metabolism disorders induced by high-fat diet in a SESN2/JNK-independent manner
复制标题
运动以不依赖SESN2/JNK的方式改善高脂饮食引起的脂质代谢紊乱
DOI：
10.1139/apnm-2021-0241
复制
发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Fu Li
中科院分区：
文献类型：
--
作者：
Wang Tianyi;Hu Wenqing;Niu Yanmei;Liu Sujuan;Fu Li
SESN 2和JNK是新出现的在调节脂质代谢中的强有力的应激诱导蛋白。本研究的目的是确定SESN 2/JNK信号通路在运动中改善高脂饮食（HFD）诱导的脂质紊乱的潜在机制。我们的数据显示，HFD和SESN 2敲除导致异常，包括体重增加，脂肪量增加，血清总胆固醇，脂质生物合成相关蛋白，以及伴随的pJNK-Thr 183/Tyr 185增加。运动训练可逆转上述变化。棕榈酸处理的C2 C12中的SESN 2沉默或JNK抑制进一步证实了SESN 2和JNK在脂质生物合成中起重要作用。拯救实验进一步证明SESN 2通过抑制JNK来减少脂质生物合成。SESN 2/JNK信号转导轴在具有由HFD或棕榈酸酯处理诱导的脂质代谢异常的动物和细胞模型中调节脂质生物合成。本研究为运动改善HFD喂养或SESN 2基因敲除诱导的脂质代谢紊乱提供了证据。新奇：运动改善HFD喂养和SESN 2基因敲除诱导的脂质代谢紊乱，SESN 2和JNK在体内外的脂质合成中起重要作用，SESN 2通过抑制JNK改善骨骼肌细胞的脂质代谢。
SESN2 and JNK are emerging powerful stress-inducible proteins in regulating lipid metabolism. The aim of this study was to determine the underlying mechanism of SESN2/JNK signaling in exercise to improve lipid disorder induced by high-fat diet (HFD). Our data showed that HFD and SESN2 knockout resulted in abnormalities including elevated body weight, increased fat mass, serum total cholesterol, lipid biosynthesis related proteins, and a concomitant increase of pJNK-Thr183/Tyr185. The above changes were reversed by exercise training. SESN2 silencing or JNK inhibition in palmitate-treated C2C12 further confirmed that SESN2 and JNK play a vital role in lipid biosynthesis. Rescue experiment further demonstrated that SESN2 reduced lipid biosynthesis through inhibition of JNK. SESN2/JNK signaling axis regulates lipid biosynthesis in both animal and cell models with abnormalities of lipid metabolism induced by HFD or palmitate treatment. This study provided evidence that exercise ameliorated lipid metabolic disorder induced by HFD feeding or by SESN2 knockout. SESN2 may improve lipid metabolism through inhibition JNK expression in skeletal muscle cells, providing a molecular mechanism that may represent an attractive target for the treatment of lipid disorder.Novelty:Exercise improved lipid disorder induced by HFD feeding and SESN2 knockout.SESN2 and JNK play a vital role in lipid biosynthesis in vivo and in vitro.SESN2 suppressed JNK to improve lipid metabolism in skeletal muscle cells.