Exercise and dietary intervention ameliorate high-fat diet-induced NAFLD and liver aging by inducing lipophagy
| Autor: | Hua Bai, Wei Zhang, Jia Li, Congwen Fang, Yu Gao, Geng-Yao Zhou, Li-Qin Zeng, Xu-Jun Qin, Jian Zhou, Feng Wang |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Aging FGF21 Clinical Biochemistry Lipophagy Diet High-Fat Biochemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Non-alcoholic Fatty Liver Disease Lipid droplet Internal medicine Nonalcoholic fatty liver disease medicine Autophagy Humans Exercise lcsh:QH301-705.5 PI3K/AKT/mTOR pathway lcsh:R5-920 Triglyceride business.industry Organic Chemistry AMPK Skeletal muscle Lipid metabolism medicine.disease Lipid Metabolism 030104 developmental biology Endocrinology medicine.anatomical_structure chemistry Liver lcsh:Biology (General) business lcsh:Medicine (General) 030217 neurology & neurosurgery Research Paper Nonalcoholic fatty liver disease (NAFLD) |
| Zdroj: | Redox Biology, Vol 36, Iss, Pp 101635-(2020) Redox Biology |
| ISSN: | 2213-2317 |
| Popis: | Exercise and dietary intervention are currently available strategies to treat nonalcoholic fatty liver disease (NAFLD), while the underlying mechanism remains controversial. Emerging evidence shows that lipophagy is involved in the inhibition of the lipid droplets accumulation. However, it is still unclear if exercise and dietary intervention improve NAFLD through regulating lipophagy, and how exercise of skeletal muscle can modulate lipid metabolism in liver. Moreover, NAFLD is associated with aging, and little is known about the effect of lipid accumulation on aging process. Here in vivo and in vitro models, we found that exercise and dietary intervention reduced lipid droplets formation, decreased hepatic triglyceride in the liver induced by high-fat diet. Exercise and dietary intervention enhanced the lipophagy by activating AMPK/ULK1 and inhibiting Akt/mTOR/ULK1 pathways respectively. Furthermore, exercise stimulated FGF21 production in the muscle, followed by secretion to the circulation to promote the lipophagy in the liver via an AMPK-dependent pathway. Importantly, for the first time, we demonstrated that lipid accumulation exacerbated liver aging, which was ameliorated by exercise and dietary intervention through inducing lipophagy. Our findings suggested a new mechanism of exercise and dietary intervention to improve NAFLD through promoting lipophagy. The study also provided evidence to support that muscle exercise is beneficial to other metabolic organs such as liver. The FGF21-mediated AMPK dependent lipophagy might be a potential drug target for NAFLD and aging caused by lipid metabolic dysfunction. Graphical abstract Image 1 |
| Databáze: | OpenAIRE |
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