Fig. 7. Proposed mechanism of TRF in Drosophila skeletal muscle under obesogenic challenges.

12 h feeding: 12 h fasting mediated TRF intervention modulates common and distinct pathways in the diet- and genetic-induced obesity models. TRF induces the upregulation of Gnmt, Sardh, and CG5955 and the downregulation of Dgat2 in both HFD and Sk2 obesity models. In HFD model, TRF induces upregulation in genes and increases in metabolites related to the purine cycle. Upregulations in the gene expression of Gnmt, Sardh and purine-cycle associated genes are potentially promoted by Crtc. In Sk2 model, upregulation of genes and increases in metabolites relating to glycolysis, glycogen metabolism, tricarboxylic acid cycle (TCA), and electron transport chain (ETC) connected by AMP kinase (AMPK) signaling are observed under TRF. Upregulation in the gene expression of Gnmt is potentially promoted by FoxO, while activation of AMPK may sustain the activation of FOXO. TRF-mediated activation of the purine cycle and AMPK signaling result in higher ATP levels which potentially lead to improved muscle performance in obesity models.