Time-restricted feeding promotes muscle function through purine cycle and AMPK signaling in Drosophila obesity models.

Autor: Livelo C; Department of Pathology, Division of Molecular and Cellular Pathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA., Guo Y; Department of Pathology, Division of Molecular and Cellular Pathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA., Abou Daya F; Department of Pathology, Division of Molecular and Cellular Pathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA., Rajasekaran V; Department of Pathology, Division of Molecular and Cellular Pathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA., Varshney S; Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, 92037, USA.; Department of Biology, Molecular Biology Institute, San Diego State University, San Diego, CA, 92182, USA., Le HD; Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, 92037, USA., Barnes S; Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA., Panda S; Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, 92037, USA., Melkani GC; Department of Pathology, Division of Molecular and Cellular Pathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA. girishmelkani@uabmc.edu.; Department of Biology, Molecular Biology Institute, San Diego State University, San Diego, CA, 92182, USA. girishmelkani@uabmc.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Feb 21; Vol. 14 (1), pp. 949. Date of Electronic Publication: 2023 Feb 21.
DOI: 10.1038/s41467-023-36474-4
Abstrakt: Obesity caused by genetic and environmental factors can lead to compromised skeletal muscle function. Time-restricted feeding (TRF) has been shown to prevent muscle function decline from obesogenic challenges; however, its mechanism remains unclear. Here we demonstrate that TRF upregulates genes involved in glycine production (Sardh and CG5955) and utilization (Gnmt), while Dgat2, involved in triglyceride synthesis is downregulated in Drosophila models of diet- and genetic-induced obesity. Muscle-specific knockdown of Gnmt, Sardh, and CG5955 lead to muscle dysfunction, ectopic lipid accumulation, and loss of TRF-mediated benefits, while knockdown of Dgat2 retains muscle function during aging and reduces ectopic lipid accumulation. Further analyses demonstrate that TRF upregulates the purine cycle in a diet-induced obesity model and AMPK signaling-associated pathways in a genetic-induced obesity model. Overall, our data suggest that TRF improves muscle function through modulations of common and distinct pathways under different obesogenic challenges and provides potential targets for obesity treatments.
(© 2023. The Author(s).)
Databáze: MEDLINE
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