Time-restricted feeding mitigates HFD-induced sarcopenic obesity in aging mice through improving the sensitivity of FGF21

Mar 7, 2025The Journal of nutritional biochemistry

Time-limited eating reduces high-fat diet-related muscle loss and obesity in aging mice by improving response to a metabolic hormone

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Abstract

Time-restricted feeding (TRF) significantly reduced global fat mass in mice and resulted in a substantial weight loss in humans.

TRF reduced global fat mass in mice with a high-fat diet, with statistical significance (P < .001).
Lean mass increased in mice undergoing TRF compared to those with ad libitum access to food.
TRF improved metabolic mobility in treated mice compared to controls.
In humans, TRF led to significant reductions in weight (P < .001) and body fat levels (P < .001).
TRF decreased serum glucose, insulin, and total cholesterol levels in obese individuals, all with high statistical significance.
The intervention may enhance liver expression of FGF21, improving its sensitivity in adipose and muscle tissues.

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Time-restricted feeding (TRF) is a dietary intervention that has been shown to have numerous health benefits. However, it is important to further investigate the potential effectiveness of TRF in addressing sarcopenic obesity (SO), which is characterized by a combination of age-related obesity and sarcopenia. In this study, 14-month-old C57BL/6J male mice were fed either regular chow diet or high-fat diet (HFD), and had either ad libitum or restricted access to food for 8 hours daily (Intervention for 7 months). For the human trial (ChiCTR2100052876), obese individuals (n=21) with a Body Mass Index ≥28 were recruited and instructed to adopt an 8-hour eating window and a 16-hour fasting period. Here, we found that the TRF intervention significantly reduced global fat mass (P < .001) and volume (P < .05), and increase lean mass compared to mice fed with HFD. Furthermore, TRF improved overall metabolic mobility (8h TRF+HFD vs. AL+HFD). This intervention also enhanced liver FGF21 protein levels (P < .01) and the expression of FGFR1 and FGF21 target genes in adipose and muscle tissues, thus improving mitochondrial quality control in these tissues. Notably, TRF interventions led to a significant decrease in serum FGF21 levels (P < .05). In the human trial, TRF intervention resulted in a significant reduction in weight (P < .001) and body fat levels (P < .001) among obese individuals, as well as a decrease in serum GLU (P < .001), insulin (P < .001), and TC levels (P < .05). Overall, the findings indicate that TRF intervention improves SO by regulating liver FGF21 expression, thereby enhancing FGF21 sensitivity in adipose and muscle tissues.

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Time-restricted feeding mitigates HFD-induced sarcopenic obesity in aging mice through improving the sensitivity of FGF21

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