Time-controlled fasting prevents aging-like mitochondrial changes induced by persistent dietary fat overload in skeletal muscle

Abstract

A large body of evidence suggests that persistent dietary fat overload causes mitochondrial dysfunction and systemic metabolic gridlock. Mitochondrial and lipid metabolism in skeletal muscle (SkM) are severely affected upon persistent high fat diet (HFD) leading to premature tissue aging. Here, we designed weekly cycles of fasting (called as time-controlled fasting, TCF) and showed that they were effective in limiting mitochondrial damage and metabolic disturbances induced by HFD. Specifically, TCF was able to prevent the decline of adipose triglyceride lipase (Atgl), maintain efficient mitochondrial respiration in SkM as well as improve blood glucose and lipid profile. Atgl was found to be the mediator of such preventive effects as its downregulation or up-regulation in C2C12 myotubes triggers mitochondrial alteration or protects against the deleterious effects of high fat levels respectively. In conclusion, TCF could represent an effective strategy to limit mitochondrial impairment and metabolic inflexibility that are typically induced by modern western diets or during aging.

Frataxin deficiency induces lipid accumulation and affects thermogenesis in brown adipose tissue

“…Indirect calorimetry performed using LabMaster (TSE Systems, Bad Homburg, Germany) as previously described 67 . Oxygen consumption (VO2), carbon dioxide production (VCO 2 ), and REE were recorded every 15 min for 24 h, and the data were averaged for each mouse.…”

“…SVCs were isolated from subcutaneous adipose tissue and differentiated in brown-like adipocytes according to Aune et al 36 . Oil Red O was used to detect intracellular triglycerides content as previously described 67 . MEFs were prepared from embryos at E13.5 as previously described 69 .…”

Chrysanthemi Zawadskii var. Latilobum Attenuates Obesity-Induced Skeletal Muscle Atrophy via Regulation of PRMTs in Skeletal Muscle of Mice

“…Several studies have shown that skeletal muscle from obese mice exhibits reduced citrate synthase activity and those of several complexes of the electron transport chain, as well as decreased oxygen consumption and ATP production [21][22][23]. To investigate the effect of CZH on mitochondrial function, we measured the mitochondrial DNA (mtDNA) content and the activities of citrate synthases and mitochondrial respiratory complexes I and II in the skeletal muscle.…”

Frataxin deficiency induces lipid accumulation and affects thermogenesis in brown adipose tissue

“…Indirect calorimetry performed using LabMaster (TSE Systems, Bad Homburg, Germany) as 385 previously described (Lettieri- Barbato et al, 2018). Oxygen consumption (VO2), carbon dioxide 386 production (VCO2) and Resting energy expenditure (REE) were recorded every 15 min for 24h, and 387 the data were averaged for each mouse.…”

“…After antigen retrieval with Citrate Buffer (pH 6.0), 395 sections were incubated at room temperature with the following primary antibodies: rabbit polyclonal 396 antibody anti-Perilipin diluted 1:1000 (9349T, Cell Signalling Technology) and rabbit polyclonal 397 antibody anti-phospho-PKA substrates diluted 1:100 (9621S, Cell Signalling Technology). Negative intracellular triglycerides content as previously described (Lettieri- Barbato et al, 2018). 424…”