Supplementation with dietary ω‐3 mitigates immobilization‐induced reductions in skeletal muscle mitochondrial respiration in young women

Abstract

Omega‐3 (ω‐3) supplementation attenuates immobilization‐induced atrophy; however, the underlying mechanisms remain unclear. Since mitochondrial dysfunction and oxidative stress have been implicated in muscle atrophy, we examined whether ω‐3 supplementation could mitigate disuse‐mediated mitochondrial dysfunction. Healthy young women (age = 22 ± 3 yr) randomly received control (n = 9) or ω‐3 supplementation (n = 11; 3 g eicosapentaenoic acid, 2 g docosahexaenoic acid) for 4 wk prior to and throughout 2 wk of single‐limb immobilization. Biopsies were performed before and after 3 and 14 d of immobilization for the assessment of mitochondrial respiration, H2O2 emission, and markers of ADP transport/lipid metabolism. In controls, immobilization rapidly (3 d) reduced (∼20%) ADP‐stimulated mitochondrial respiration without altering ADP sensitivity or the abundance of mitochondrial proteins. Extending immobilization to 14 d did not further reduce mitochondrial coupled respiration; however, unlike following 3 d, mitochondrial proteins were reduced ∼20%. In contrast, ω‐3 supplementation prevented immobilization‐induced reductions in mitochondrial content and respiration throughout the immobilization period. Regardless of dietary supplement, immobilization did not alter mitochondrial H2O2 emission in the presence or absence of ADP, markers of cellular redox state, mitochondrial lipid–supported respiration, or lipid‐related metabolic proteins. These data highlight the rapidity of mitochondrial adaptations in response to muscle disuse, challenge the necessity for increased oxidative stress during inactivity, and establish that ω‐3 supplementation preserves oxidative phosphorylation function and content during immobilization.—Miotto, P. M., McGlory, C., Bahniwal, R., Kamal, M., Phillips, S. M., Holloway, G. P. Supplementation with dietary ω‐3 mitigates immobilization‐induced reductions in skeletal muscle mitochondrial respiration in young women. FASEB J. 33, 8232–8240 (2019). http://www.fasebj.org

Short‐term bed rest‐induced insulin resistance cannot be explained by increased mitochondrial H2O2 emission

“…), and our recent work highlighting that leg immobilization rapidly impairs mitochondrial respiratory capacity in as little as 3 days (Miotto et al . ). In the present study, the reduction in respiratory capacity coincided with a reduction in OXPHOS proteins.…”

“…; Miotto et al . ). While these data suggest temporally oxidative phosphorylation is impaired, inducing mitophagy, in contrast, a recent report has also shown that 4 days of strict bed rest reduced mitochondrial content in the absence of a reduction in respiratory capacity (Larsen et al .…”

“…While it is tempting to speculate a causative relationship between these observations, our previous work has highlighted that muscle disuse impairs respiration before a reduction in OXPHOS protein (Miotto et al . ), strongly suggesting rapid post‐translational modifications of the electron transport contribute to the observed impairment in respiratory capacity. While mitophagy probably contributes to the subsequent reduction in mitochondrial proteins (Miotto et al .…”

“…While mitophagy probably contributes to the subsequent reduction in mitochondrial proteins (Miotto et al . ), the half‐life of mitochondrial proteins has been estimated to be ∼14 days (Menzies & Gold, ), suggesting subtle changes in mitochondrial content before this time may be difficult to detect. This probably accounts for muscle disuse/detraining studies yielding inconsistent findings regarding decrements in markers of mitochondrial content within 7 days (Coyle et al .…”

Are Alterations in Skeletal Muscle Mitochondria a Cause or Consequence of Insulin Resistance?

“…Although, when mitochondrial respiration was normalised to CS activity these decreases were no longer statistically different [56]. Despite this, single leg immobilization decreases respiration before any changes in the expression of components of the respiratory chain [104]. This suggests that changes in mitochondrial respiratory function may occur prior to changes in content, which may take a longer time to occur.…”