Intermittent fasting activates macrophage migration inhibitory factor and alleviates high-fat diet-induced nonalcoholic fatty liver disease.
Intermittent fasting activates macrophage migration inhibitory factor and alleviates high-fat diet-induced nonalcoholic fatty liver disease.
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DOI：
10.1038/s41598-023-40373-5
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发表时间：
2023-08-11
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
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转为正常饮食（ND）是高脂饮食（HFD）诱导的非酒精性脂肪性肝病（NAFLD）的常规治疗。间歇性禁食（IF）是一种独特的治疗方法，可能会显示出更好的治疗效果。因此，我们的目的是研究这些治疗方法的治疗效果，并探讨其机制。在本研究中，通过10周的HFD诱导NAFLD小鼠模型。此后，小鼠在接下来的12周内采用持续的HFD、ND或IF。最后，然后收获肝脏以评估脂质沉积、脂质代谢、细胞凋亡和自噬，同时收集血液以测定血糖和胰岛素。结果表明，IF和ND治疗可改善NAFLD小鼠的脂质沉积和代谢紊乱，减轻HFD小鼠体重、肝重和HOMA-IR指数的增加。此外，IF和ND处理激活了巨噬细胞移动抑制因子（MIF）/AMPK通路，并调节其下游的自噬和凋亡。但IF的疗效优于ND。IF和ND都能激活MIF信号通路并减轻NAFLD的脂毒性，而IF治疗比ND更有效。不同的MIF上调可能是IF比ND更有益的潜在机制。
Switching to normal diet (ND) is the regular therapy for high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD). Intermittent fasting (IF) is a unique treatment which may exhibits better therapeutic efficacy. Thus, we aim to investigate the therapeutic effects of these treatments and exploring the mechanisms. In the present study, NAFLD mouse model was induced by a 10-week HFD. Thereafter, mice adopted continued HFD, ND, or IF for the next 12 weeks. Finally, the liver was then harvested to assess lipid deposition, lipid metabolism, apoptosis, and autophagy, while blood was collected to determine blood glucose and insulin. The results showed that IF and ND treatment improved lipid deposition and metabolic disorder of NAFLD mice; the increasing body weight, liver weight, and HOMA-IR index of HFD mice were also alleviated by IF and ND. Furthermore, IF and ND treatment activated the macrophage migration inhibitory factor (MIF)/AMPK pathway and regulated its downstream autophagy and apoptosis. However, the efficacy of IF was better than ND. Both IF and ND activates MIF signaling and alleviate the lipotoxicity of NAFLD while IF therapy is more effective than ND. The different MIF up-regulation might be the underlying mechanism of why IF benefits more than ND.
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