Dietary restriction increases skeletal muscle mitochondrial respiration but not mitochondrial content in C57BL/6 mice

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.

Late-onset caloric restriction alters skeletal muscle metabolism by modulating pyruvate metabolism

“…Mitochondrial dysfunction likely contributed to this metabolic shift. Consistent with previous reports that mitochondrial function declines with aging (16,21,25), we found that the OCR in muscles of older rats was only 60% of that in young rats under basal conditions. Compared with OXPHOS, glycolysis is a less efficient way to generate ATP; thus, aging muscles may experience ATP deficiency when they have impaired mitochondrial function and depend more on glycolysis as the energy source.…”

“…The simultaneous determination of OXPHOS and glycolysis enables the elucidation of the shift between these two pathways with aging and after interventions. Using this new technology, we tested the first hypothesis of this study, that the CR-induced positive effects on muscle mass are associated with an improvement in cellular metabolism.To date, most studies have focused on examining the effects of "life-long" CR, where CR was initiated when animals were still growing and the effects were evaluated when the animals were at an advanced age (16,25,34). Recently, it has been suggested that the effects of CR are age dependent.…”

“…Caloric-restricted animals were previously found to have improved mitochondrial function characterized by increased oxygen consumption (16,25). The benefits of CR for glycolysis and the cellular dependency on OXPHOS or glycolysis are not known.…”

“…To date, most studies have focused on examining the effects of "life-long" CR, where CR was initiated when animals were still growing and the effects were evaluated when the animals were at an advanced age (16,25,34). Recently, it has been suggested that the effects of CR are age dependent.…”

Sterol regulatory element-binding protein-1c orchestrates metabolic remodeling of white adipose tissue by caloric restriction

“…These findings are inconsistent with a previous report that CR enhanced mitochondrial biogenesis in various tissues, including WAT and liver (Nisoli et al ., 2005). In contrast to that, however, certain reports suggested that CR did not induce mitochondrial biogenesis or increase mitochondrial content (Hempenstall et al ., 2012; Lanza et al ., 2012). Although the reasons for these discrepancies are unclear, they might result from differences in experimental conditions, including onset age or duration of CR, strain backgrounds of mice, diet components, and housing environments.…”