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

Apr 6, 2023FASEB journal : official publication of the Federation of American Societies for Experimental Biology

Liver-made FGF21 is needed for time-limited eating to reduce fatty liver caused by a high-fat diet in mice

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Abstract

Serum FGF21 levels were significantly increased after 16 weeks of time-restricted feeding.

Time-restricted feeding (TRF) prevented body weight gain and improved glucose regulation.
TRF protected against liver fat accumulation and damage caused by a high-fat diet.
Gene expression related to liver fat production and inflammation decreased with TRF, while genes involved in fat breakdown increased.
The benefits of TRF were diminished in mice lacking liver FGF21 signaling.
TRF also enhanced insulin sensitivity and reduced liver damage in mice with diet-induced obesity.

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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.

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

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