Liver‐derived FGF21 is required for the effect of time‐restricted feeding on high‐fat diet‐induced fatty liver in mice

作者：Lun Hua, Jing Li, Yi Yang, Dandan Jiang, Xuemei Jiang, Xingfa Han, Chao Jin, Bin Feng, Lianqiang Che, Shengyu Xu, Yan Lin, Jian Li, Zhengfeng Fang, Mengmeng Sun, Senyan Du, Ting Luo, De Wu, Yong Zhuo · 发表于：The FASEB Journal · 年份：2023 · DOI：10.1096/fj.202202031r · 被引用次数：13 · 研究领域：Fibroblast Growth Factor Research、Dietary Effects on Health、Liver Disease Diagnosis and Treatment

Nonalcoholic fatty liver disease (NAFLD), which leads to insulin resistance, steatosis, and even hepatocellular carcinoma, is the most common chronic liver disease worldwide, however, effective treatment is still lacking. This study determined the role of liver FGF21 and the mechanisms underlying the protective effects of time-restricted feeding (TRF) in NAFLD. FGF21 liver knockout (FGF21 LKO) mice and C57BL/6 wild-type (WT) mice were fed either a normal or a high-fat diet (HFD) for 16 weeks. Mice with diet-induced obesity (DIO) were also used. The mice were fed either ad libitum or in a time-restricted manner. Serum FGF21 levels were significantly increased after 16 weeks of TRF. TRF prevented body weight gain, improved glucose homeostasis, and protected against high-fat diet-induced hepatosteatosis and liver damage. The expression of genes related to liver lipogenesis and inflammation was reduced in TRF mice, but the expression of genes involved in fatty acid β-oxidation was increased. However, those beneficial effects of TRF were blunted in the FGF21 LKO mice. Moreover, TRF promoted improvements in insulin sensitivity and liver damage in DIO mice. Our data show that liver FGF21 signaling was involved in the effect of TRF on high-fat diet-induced fatty liver.