Stem Cell and Biotherapy Engineering Research Center of Henan, College of Medical Engineering, Xinxiang Medical University, East of JinSui Road #601, Xinxiang City, 453003, Henan Province, China.
Henan Joint International Research Laboratory of Stem Cell Medicine, Xinxiang Medical University, Xinxiang, 453003, China.
Mol Biol Rep. 2022 Apr;49(4):3113-3122. doi: 10.1007/s11033-022-07142-5. Epub 2022 Feb 2.
Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that ultimately leads to cirrhosis and hepatocellular carcinoma. Intermittent fasting has been proposed as a nonpharmacological dietary approach against metabolic diseases, including NAFLD. In this study, we aimed to investigate the effect of alternate day fasting (ADF) on high-fat diet (HFD)-induced NAFLD in C57BL/6 mice.
A mouse model of fatty liver disease was established by feeding the mice a HFD for 16 weeks. The mice were administered by body weight, lipid accumulation and inflammation. PPARα, FGF21, serum triglycerides (TG), total cholesterol (TC), transaminase and lipogenesis were assessed.
The results showed that long-term ADF can attenuate fatty liver disease by reducing hepatic inflammation and lipid accumulation in a mouse model. Meanwhile, fasting elevated the expression of serum and hepatic fibroblast growth Factor 21 (Fgf21), a circulating hormone produced predominantly in the liver, and could effectively prevent and ameliorate the pathogenesis of NAFLD. Serum starvation also enhanced Fgf21 expression and reduced free fatty acid (FFA)-induced lipid storage in hepatocytes. Moreover, refeeding inhibited the increase in Fgf21 expression induced by fasting. This fasted-to-refed transition is closely related to the expression of Fgf21. Further in vitro and in vivo studies showed that fasting-sensitive PPARα is indispensable for the expression of Fgf21 and its protective effect on NAFLD.
These findings indicated that long-term ADF protects mouse livers against HFD induced fatty liver disease through controlling PPARα/Fgf21 signaling. In conclusion, ADF can emerge as a non-pharmacological dietary approach against fatty liver disease.
非酒精性脂肪性肝病（NAFLD）是一种常见的慢性肝脏疾病，最终可导致肝硬化和肝细胞癌。间歇性禁食已被提出作为一种非药物性饮食方法来对抗代谢疾病，包括 NAFLD。在这项研究中，我们旨在研究隔日禁食（ADF）对高脂肪饮食（HFD）诱导的 C57BL/6 小鼠 NAFLD 的影响。
通过用 HFD 喂养小鼠 16 周来建立脂肪肝病的小鼠模型。根据体重、脂质积累和炎症来给小鼠进行给药。评估过氧化物酶体增殖物激活受体α（PPARα）、成纤维细胞生长因子 21（FGF21）、血清甘油三酯（TG）、总胆固醇（TC）、转氨酶和脂肪生成。
结果表明，长期 ADF 可以通过减少肝脏炎症和脂质积累来减轻小鼠模型中的脂肪肝病。同时，禁食会增加血清和肝脏成纤维细胞生长因子 21（Fgf21）的表达，Fgf21 是一种主要在肝脏中产生的循环激素，可有效预防和改善 NAFLD 的发病机制。血清饥饿还增强了 Fgf21 的表达，并减少了游离脂肪酸（FFA）诱导的肝细胞脂质储存。此外，再喂养抑制了禁食诱导的 Fgf21 表达增加。这种禁食到再喂养的转变与 Fgf21 的表达密切相关。进一步的体外和体内研究表明，禁食敏感的过氧化物酶体增殖物激活受体α（PPARα）是 Fgf21 表达及其对 NAFLD 保护作用所必需的。
这些发现表明，长期 ADF 通过控制 PPARα/Fgf21 信号通路来保护小鼠肝脏免受 HFD 诱导的脂肪肝病。总之，ADF 可以作为一种非药物性饮食方法来对抗脂肪肝病。
