Tang Haiying, Tan Xiaoyan, Zhu Lei, Qin Kairong, Gao Huan, Bai Hao
Department of Biomedical Engineering, Dalian University of Technology Dalian 116024, Liaoning Province, P. R. China.
Department of Gastroenterology, The Affiliated First Hospital of Dalian Medical University Dalian 116011, Liaoning Province, P. R. China.
Am J Transl Res. 2019 Jul 15;11(7):4315-4325. eCollection 2019.
Physical inactivity is an important contributor to obesity and fat accumulation in tissues. Critical complications of obesity include type II diabetes and nonalcoholic fatty liver disease (NAFLD). Exercise has been reported to exert ameliorating effects on obesity and NAFLD. However, the underlying mechanism is not fully understood. We showed the increase of microRNA-451 (miR-451) and decrease of macrophage migration inhibitory factor (MIF) in liver, after swim training in high fat diet (HFD) mice. MIF expression was regulated by miR-451. HFD intake caused the increase of body weights in WT and MIF knockout (KO) mice. In addition, HFD-induced liver anomalies were associated with Akt activation and autophagy suppression, which were reversed by MIF KO. In hepatocytes from HFD WT and MIF KO mice, autophagy was inhibited by exogenous rmMIF through Akt activation. Meanwhile, miR-451 antagonized the regulation of MIF on Akt signaling and autophagy. Taken together, these results indicate that MIF was decreased in liver of HFD mice due to physical exercise, and might prevent hepatic steatosis by suppressing Akt signaling and promoting autophagy.
缺乏身体活动是导致肥胖和组织脂肪堆积的一个重要因素。肥胖的关键并发症包括II型糖尿病和非酒精性脂肪性肝病（NAFLD）。据报道，运动对肥胖和NAFLD具有改善作用。然而，其潜在机制尚未完全明确。我们发现，高脂饮食（HFD）小鼠进行游泳训练后，肝脏中微小RNA-451（miR-451）增加，巨噬细胞迁移抑制因子（MIF）减少。MIF的表达受miR-451调控。摄入HFD会导致野生型（WT）和MIF基因敲除（KO）小鼠体重增加。此外，HFD诱导的肝脏异常与Akt激活和自噬抑制有关，而MIF基因敲除可逆转这些异常。在HFD野生型和MIF基因敲除小鼠的肝细胞中，外源性重组小鼠MIF（rmMIF）通过激活Akt抑制自噬。同时，miR-451拮抗MIF对Akt信号传导和自噬的调控。综上所述，这些结果表明，运动导致HFD小鼠肝脏中MIF减少，MIF可能通过抑制Akt信号传导和促进自噬来预防肝脂肪变性。
