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Dietary restriction increases skeletal muscle mitochondrial respiration but not mitochondrial content in C57BL/6 mice
Authors:Hempenstall Sarah  Page Melissa M  Wallen Katrina R  Selman Colin
Affiliation:Integrative and Environmental Physiology, Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen AB24 2TZ, UK
Abstract:
Dietary restriction (DR) is suggested to induce mitochondrial biogenesis, although recently this has been challenged. Here we determined the impact of 1, 9 and 18 months of 30% DR in male C57BL/6 mice on key mitochondrial factors and on mitochondrial function in skeletal muscle, relative to age-matched ad libitum (AL) controls. We examined proteins and mRNAs associated with mitochondrial biogenesis and measured mitochondrial respiration in permeabilised myofibres using high resolution respirometry. 30% DR, irrespective of duration, had no effect on citrate synthase activity. In contrast, total and nuclear protein levels of PGC-1α, mRNA levels of several mitochondrial associated proteins (Pgc-1α, Nrf1, Core 1, Cox IV, Atps) and cytochrome c oxidase content were increased in skeletal muscle of DR mice. Furthermore, a range of mitochondrial respiration rates were increased significantly by DR, with DR partially attenuating the age-related decline in respiration observed in AL controls. Therefore, DR did not increase mitochondrial content, as determined by citrate synthase, in mouse skeletal muscle. However, it did induce a PGC-1α adaptive response and increased mitochondrial respiration. Thus, we suggest that a functionally ‘efficient’ mitochondrial electron transport chain may be a critical mechanism underlying DR, rather than any net increase in mitochondrial content per se.
Keywords:DR, dietary restriction   AL, ad libitum   FI, food intake   BM, body mass   CS, citrate synthase   COX IV, cytochrome c oxidase   HRR, high resolution respirometry   BIOPS, biopsy preservation solution   PGC-1α, peroxisome proliferator-activated receptor gamma co-activator   ETS, electron transport system   OXPHOS, oxidative phosphorylation
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