Bed rest and resistive vibration exercise unveil novel links between skeletal muscle mitochondrial function and insulin resistance

Kenny, Helena; Rudwill, Floriane; Breen, Laura; Salanova, Michele; Blottner, Dieter; Heise, Tim; Heer, Martina; Blanc, Stéphane; OʼGorman, Donal J.

doi:10.1007/s00125-017-4298-z

Cited by 48 publications

(48 citation statements)

References 49 publications

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“…In support of this, bed rest has recently been shown to decrease the protein content of the inner mitochondrial membrane ADP transporter, adenine nucleotide translocase (ANT; Kenny et al . ). Moreover, we have previously shown that the ability of submaximal ADP concentrations to decrease mitochondrial hydrogen peroxide emission is impaired in insulin‐resistant rodents (Smith et al .…”

Section: Introductionmentioning

confidence: 97%

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

Dirks

Miotto

Goossens

et al. 2019

The Journal of Physiology

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Key pointsr We determined if bed rest increased mitochondrially derived reactive oxygen species and cellular redox stress, contributing to the induction of insulin resistance.r Bed rest decreased maximal and submaximal ADP-stimulated mitochondrial respiration. r Bed rest did not alter mitochondrial H 2 O 2 emission in the presence of ADP concentrations indicative of resting muscle, the ratio of H 2 O 2 emission to mitochondrial O 2 consumption or markers of oxidative stress r The present data suggest strongly that mitochondrial H 2 O 2 does not contribute to bed rest-induced insulin resistance Abstract Mitochondrial H 2 O 2 has been causally linked to diet-induced insulin resistance, although it remains unclear if muscle disuse similarly increases mitochondrial H 2 O 2 . Therefore, we investigated the potential that an increase in skeletal muscle mitochondrial H 2 O 2 emission, potentially as a result of decreased ADP sensitivity, contributes to cellular redox stress and the induction of insulin resistance during short-term bed rest in 20 healthy males. Bed rest led to a decline in glucose infusion rate during a hyperinsulinaemic-euglycaemic clamp (−42 ± 2%; P < 0.001), and in permeabilized skeletal muscle fibres it decreased OXPHOS protein content (−16 ± 8%) and mitochondrial respiration across a range of ADP concentrations (−13 ± 5%). While bed rest tended to increase maximal mitochondrial H 2 O 2 emission rates (P = 0.053), H 2 O 2 emission in the presence of ADP concentrations indicative of resting muscle, the ratio of H 2 O 2 emission to mitochondrial O 2 consumption, and markers of oxidative stress were not altered following bed rest. Altogether, while bed rest impairs mitochondrial ADP-stimulated respiration, an increase in mitochondrial H 2 O 2 emission does not contribute to the induction of insulin resistance following short-term bed rest.Marlou Dirks is a Sir Henry Wellcome Postdoctoral Fellow in the Department of Sport and Health Sciences at the University of Exeter, UK. Her research focuses on the impact of muscle disuse on metabolic health and the regulation of skeletal muscle protein turnover. Dr Dirks applies detailed in vivo metabolic techniques in experimental models of muscle disuse (i.e. bed rest, limb immobilization) to gain mechanistic insight into disuse-induced muscle atrophy and investigate potential interventional strategies for the preservation of muscle mass and metabolic health during muscle disuse. Clinical trial registration: NCT02521025 Methods SubjectsTwenty healthy, recreationally active males (age 25 ± 1 years) were included in the present study. Subjects'

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Section: Introductionmentioning

confidence: 97%

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

Dirks

Miotto

Goossens

et al. 2019

The Journal of Physiology

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“…The lack of an association between changes in mitochondrial characteristics and insulin and glucose tolerance was further reinforced by the absence of consistent or strong correlations between these measures. Previous studies examining correlations between these measures in human participants have found correlations between mitochondrial content and insulin resistance [3], but correlations between mitochondrial respiration and insulin resistance have been less consistent [6] [42,43].…”

Section: Discussionmentioning

confidence: 94%

Changes in insulin resistance do not occur in parallel with changes in mitochondrial content and function in male rats

Genders

Kuang

et al. 2020

Preprint

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AbstractAims/hypothesisTo investigate if there is a causal relationship between changes in insulin resistance and mitochondrial respiratory function and content in rats fed a high fat diet (HFD) with or without concurrent exercise training. We hypothesised that provision of a high fat diet (HFD) would increase insulin resistance and decrease mitochondrial characteristics (content and function), and that exercise training would improve both mitochondrial characteristics and insulin resistance in rats fed a HFD.MethodsMale Wistar rats were given either a chow diet or a high fat diet (HFD) for 12 weeks. After 4 weeks of the dietary intervention, half of the rats in each group began eight weeks of interval training. In vivo glucose and insulin tolerance was assessed, as was ex vivo glucose uptake in epitrochlearis muscle. Mitochondrial respiratory function was assessed in permeabilised soleus and white gastrocnemius (WG) muscles. Mitochondrial content was determined by measurement of citrate synthase (CS) activity and protein expression of components of the electron transport system (ETS).ResultsHFD rats had impaired glucose and insulin tolerance. HFD did not change CS activity in the soleus; however, it did increase CS activity in WG (Chow 5.9 ± 0.5, HFD 7.2 ± 0.7 mol h-1 kg protein-1). Protein expression of components of the ETS and mitochondrial respiratory function (WG Chow 65.2 ± 8.4, HFD 88.6 ± 8.7 pmol O2 s-1 mg-1) were also increased by HFD. Exercise training improved glucose and insulin tolerance in the HFD rats. Exercise training did not alter CS activity in either muscle. Mitochondrial respiratory function was increased with exercise training in the chow fed animals in soleus muscle, but not in WG. This exercise effect was absent in the HFD animals. Mitochondrial characteristics did not consistently correlate with insulin or glucose tolerance.Conclusions/interpretationHFD induced insulin resistance, but it did not negatively affect any of the measured mitochondrial characteristics. Exercise training improved insulin resistance, but without changes in mitochondrial respiration and content. The lack of an association between mitochondrial characteristics and insulin resistance was reinforced by the absence of strong correlations between these measures. Our results suggest that defects in mitochondrial respiration and content are not responsible for insulin resistance in HFD rats.

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“…However, after adjusting for physical activity and/or trunk fat mass, this relationship between muscle insulin sensitivity and mitochondrial respiration was partially lost and no longer significant [98]. In a study examining bed rest (an extreme form of physical inactivity), there was a positive correlation between mitochondrial respiration and insulin sensitivity [55]. However, on further examination of these findings, this effect may have been due to changes in mitochondrial content rather than changes in respiration [55].…”

Section: Is There a Relationship Between Mitochondrial Respiratory Fumentioning

confidence: 97%

“…In a study examining bed rest (an extreme form of physical inactivity), there was a positive correlation between mitochondrial respiration and insulin sensitivity [55]. However, on further examination of these findings, this effect may have been due to changes in mitochondrial content rather than changes in respiration [55]. Therefore, although some studies have observed parallel changes in mitochondrial respiration and insulin resistance, the relationship between the two appears to be affected by other factors, such as mitochondrial content, physical activity level, and fat mass.…”

Section: Is There a Relationship Between Mitochondrial Respiratory Fumentioning

confidence: 99%

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

Genders

Holloway

Bishop

2020

IJMS

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As a major site of glucose uptake following a meal, skeletal muscle has an important role in whole-body glucose metabolism. Evidence in humans and animal models of insulin resistance and type 2 diabetes suggests that alterations in mitochondrial characteristics accompany the development of skeletal muscle insulin resistance. However, it is unclear whether changes in mitochondrial content, respiratory function, or substrate oxidation are central to the development of insulin resistance or occur in response to insulin resistance. Thus, this review will aim to evaluate the apparent conflicting information placing mitochondria as a key organelle in the development of insulin resistance in skeletal muscle.

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Bed rest and resistive vibration exercise unveil novel links between skeletal muscle mitochondrial function and insulin resistance

Cited by 48 publications

References 49 publications

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

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

Changes in insulin resistance do not occur in parallel with changes in mitochondrial content and function in male rats

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

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Bed rest and resistive vibration exercise unveil novel links between skeletal muscle mitochondrial function and insulin resistance

Cited by 48 publications

References 49 publications

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

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

Changes in insulin resistance do not occur in parallel with changes in mitochondrial content and function in male rats

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

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

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