Open AccessTime-controlled fasting prevents aging-like mitochondrial changes induced by persistent dietary fat overload in skeletal muscle
Author(s) -
Daniele Lettieri Barbato,
Stefano Cannata,
Viviana Casagrande,
Maria Rosa Ciriolo,
Katia Aquilano
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0195912
Subject(s) - endocrinology , medicine , skeletal muscle , biology , adipose triglyceride lipase , mitochondrion , downregulation and upregulation , adipose tissue , microbiology and biotechnology , biochemistry , lipolysis , gene
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.