Alternate-day fasting alleviates high fat diet induced non-alcoholic fatty liver disease through controlling PPARα/Fgf21 signaling.

Autor: Liu X; 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., Zhang Y; 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., Ma C; 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., Lin J; 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. linjtlin@126.com.; Henan Joint International Research Laboratory of Stem Cell Medicine, Xinxiang Medical University, Xinxiang, 453003, China. linjtlin@126.com., Du J; 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. dujiang538@126.com.; Henan Joint International Research Laboratory of Stem Cell Medicine, Xinxiang Medical University, Xinxiang, 453003, China. dujiang538@126.com.
Jazyk: angličtina
Zdroj: Molecular biology reports [Mol Biol Rep] 2022 Apr; Vol. 49 (4), pp. 3113-3122. Date of Electronic Publication: 2022 Feb 02.
DOI: 10.1007/s11033-022-07142-5
Abstrakt: Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
(© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)
Databáze: MEDLINE