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

Christopher Livelo, Yiming Guo, Farah Abou Daya, Vasanthi Rajasekaran, Shweta Varshney, Hiep D. Le, Stephen Barnes, Satchidananda Panda and Girish C. Melkani ()
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Christopher Livelo: University of Alabama at Birmingham
Yiming Guo: University of Alabama at Birmingham
Farah Abou Daya: University of Alabama at Birmingham
Vasanthi Rajasekaran: University of Alabama at Birmingham
Shweta Varshney: Salk Institute for Biological Studies
Hiep D. Le: Salk Institute for Biological Studies
Stephen Barnes: University of Alabama at Birmingham
Satchidananda Panda: Salk Institute for Biological Studies
Girish C. Melkani: University of Alabama at Birmingham

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-36474-4

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