2. Academic Validation
  3. Time-restricted feeding mitigates HFD-induced sarcopenic obesity in aging mice through improving the sensitivity of FGF21

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

  • J Nutr Biochem. 2025 Mar 5:140:109893. doi: 10.1016/j.jnutbio.2025.109893.
Ting Wang 1,  Hongkun Lin 2,  Yan Deng 3,  Wenwen Chen 3,  Yangliu Xu 3,  Li Wang 3,  Aojia Zhou 3,  Yidan Zhang 3,  Ziping Wang 3,  Xin Jin 4,  Li Zhang 5,  Xin Wang 3,  Yang Zhou 2,  Ruhan Wang 3,  Shuang Rong 6
Affiliations

Affiliations

  • 1 Academy of Nutrition and Health, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Public Health, Wuhan University of Science and Technology, Wuhan, China; Institute of Pharmaceutical Process, Department of Pharmacy, College of Medicine, Wuhan University of Science and Technology, Wuhan, China.
  • 2 Department of Food and Nutrition Health, School of Public Health, Wuhan University, Wuhan, China.
  • 3 Academy of Nutrition and Health, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Public Health, Wuhan University of Science and Technology, Wuhan, China.
  • 4 Academy of Nutrition and Health, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Public Health, Wuhan University of Science and Technology, Wuhan, China; Department of Clinical Nutrition, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • 5 Academy of Nutrition and Health, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Public Health, Wuhan University of Science and Technology, Wuhan, China; Xinhua Hospital of Hubei University of Chinese Medicine, Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Wuhan, China.
  • 6 Academy of Nutrition and Health, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Public Health, Wuhan University of Science and Technology, Wuhan, China; Department of Food and Nutrition Health, School of Public Health, Wuhan University, Wuhan, China. Electronic address: rongshuang@whu.edu.cn.
PMID: 40054671 DOI: 10.1016/j.jnutbio.2025.109893
Abstract

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.

Keywords

Aging; FGF21; Mitochondria; Sarcopenic obesity; Time-restricted feeding.

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