scholarly journals Human, donkey and cow milk differently affects insulin sensitivity by modulating skeletal muscle mitochondrial function, efficiency and dynamics

2016 ◽  
Vol 1857 ◽  
pp. e100-e101
Author(s):  
Giovanna Trinchese ◽  
Gina Cavaliere ◽  
Chiara De Filippo ◽  
Anna De Angelis ◽  
Antonio Della Gatta ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Mitochondrial Function ◽  
Cow Milk

scholarly journals Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans

2020 ◽  
Vol 112 (2) ◽  
pp. 413-426 ◽  
Author(s):  
Carlijn M E Remie ◽  
Kay H M Roumans ◽  
Michiel P B Moonen ◽  
Niels J Connell ◽  
Bas Havekes ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Composition ◽  
Insulin Sensitivity ◽  
Energy Metabolism ◽  
Mitochondrial Function ◽  
Dry Weight ◽  
Metabolic Health ◽  
Men And Women ◽  
Nicotinamide Riboside ◽  
Wet Weight

ABSTRACT Background Nicotinamide riboside (NR) is an NAD+ precursor that boosts cellular NAD+ concentrations. Preclinical studies have shown profound metabolic health effects after NR supplementation. Objectives We aimed to investigate the effects of 6 wk NR supplementation on insulin sensitivity, mitochondrial function, and other metabolic health parameters in overweight and obese volunteers. Methods A randomized, double-blinded, placebo-controlled, crossover intervention study was conducted in 13 healthy overweight or obese men and women. Participants received 6 wk NR (1000 mg/d) and placebo supplementation, followed by broad metabolic phenotyping, including hyperinsulinemic-euglycemic clamps, magnetic resonance spectroscopy, muscle biopsies, and assessment of ex vivo mitochondrial function and in vivo energy metabolism. Results Markers of increased NAD+ synthesis—nicotinic acid adenine dinucleotide and methyl nicotinamide—were elevated in skeletal muscle after NR compared with placebo. NR increased body fat-free mass (62.65% ± 2.49% compared with 61.32% ± 2.58% in NR and placebo, respectively; change: 1.34% ± 0.50%, P = 0.02) and increased sleeping metabolic rate. Interestingly, acetylcarnitine concentrations in skeletal muscle were increased upon NR (4558 ± 749 compared with 3025 ± 316 pmol/mg dry weight in NR and placebo, respectively; change: 1533 ± 683 pmol/mg dry weight, P = 0.04) and the capacity to form acetylcarnitine upon exercise was higher in NR than in placebo (2.99 ± 0.30 compared with 2.40 ± 0.33 mmol/kg wet weight; change: 0.53 ± 0.21 mmol/kg wet weight, P = 0.01). However, no effects of NR were found on insulin sensitivity, mitochondrial function, hepatic and intramyocellular lipid accumulation, cardiac energy status, cardiac ejection fraction, ambulatory blood pressure, plasma markers of inflammation, or energy metabolism. Conclusions NR supplementation of 1000 mg/d for 6 wk in healthy overweight or obese men and women increased skeletal muscle NAD+ metabolites, affected skeletal muscle acetylcarnitine metabolism, and induced minor changes in body composition and sleeping metabolic rate. However, no other metabolic health effects were observed. This trial was registered at clinicaltrials.gov as NCT02835664

scholarly journals Eicosapentaenoic Acid-Induced Inhibition of Metabolic Inflammation Is Associated with Preserved Mitochondrial Function and Insulin Sensitivity in Human Primary Myotubes

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 471-471
Author(s):  
Domenico Sergi ◽  
Natalie Luscombe-Marsh ◽  
Leonie Kaye Heilbronn ◽  
Mark Birch-Machin ◽  
Christopher Proud ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Eicosapentaenoic Acid ◽  
Mitochondrial Function ◽  
Core Protein ◽  
Mitochondrial Dynamics ◽  
Complex Iii ◽  
Nuclear Factor ◽  
Metabolic Inflammation ◽  
Nuclear Factor Kappa

Abstract Objectives The aim of this study was to investigate whether metabolic inflammation in skeletal muscle may be prevented by eicosapentaenoic acid (EPA) and if this is associated with an improvement in markers of mitochondrial function and insulin sensitivity. Methods Human primary myotubes were treated for 24 hours with palmitic acid (PA, 500 µM) in hyperglycaemic conditions (13 mM glucose), referred to as nutrient overload, in the presence or absence of EPA (100 µM). After the treatments, the expression of peroxisome proliferator-activated receptor-γ coactivator 1-alpha (PGC1α) and interleukin-6 (IL-6) was assessed by q-PCR. Western blot was used to asses the abundance of the inhibitor of nuclear factor kappa-B (IKBα), mitochondrial electron transport chain complex proteins, the phosphorylation of AKT (Ser473) and AKT substrate 160 (AS 160) (Thr642) in response to insulin, the activation of 5'-AMP-activated protein kinase (AMPK) and the inhibition of acetyl-CoA carboxylase (ACC). Mitochondrial dynamics was assessed by immunocytochemistry. Results Nutrient excess activated the proinflammatory nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) signalling as indicated by the upregulation of IL-6 mRNA (P < 0.001) and a tendency to decrease in IKBα (P = 0.0654), tended to downregulate PGC1α (P = 0.0589) and promoted mitochondrial fragmentation (P < 0.001), all of which were counteracted by EPA. Furthermore, EPA induced complex III-core protein 2 (P < 0.05) relative to control cells, an effect that was absent in the myotubes exposed only to PA and hyperglycaemia. EPA, when administrated in combination with PA and hyperglycaemia, induced the phosphorylation of AMPK (P < 0.05) and its downstream target ACC (P < 0.05) relative to cells exposed to nutrient overload alone. Finally, while fuel surplus impaired insulin-induced phosphorylation of AKT (P < 0.01) and AS160 (P < 0.05), these effects were prevented by EPA. Conclusions EPA inhibited NFkB signalling which was associated with an attenuation of the deleterious effects of PA and hyperglycaemia on markers of mitochondrial function and insulin sensitivity. Thus, EPA may represent a valuable nutritional tool to preserve skeletal muscle mitochondrial function and metabolic health during periods of nutrient overload. Funding Sources CSIRO's Precision Health Future Science Platform (FSP).

PGC-1α-mediated regulation of mitochondrial function and physiological implications

2020 ◽  
Vol 45 (9) ◽  
pp. 927-936
Author(s):  
Jens Frey Halling ◽  
Henriette Pilegaard
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Function ◽  
Current Evidence ◽  
Peroxisome Proliferator ◽  
Control Mechanisms ◽  
Peroxisome Proliferator Activated Receptor ◽  
Age Related ◽  
Mitochondrial Functions

The majority of human energy metabolism occurs in skeletal muscle mitochondria emphasizing the importance of understanding the regulation of myocellular mitochondrial function. The transcriptional co-activator peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) has been characterized as a major factor in the transcriptional control of several mitochondrial components. Thus, PGC-1α is often described as a master regulator of mitochondrial biogenesis as well as a central player in regulating the antioxidant defense. However, accumulating evidence suggests that PGC-1α is also involved in the complex regulation of mitochondrial quality beyond biogenesis, which includes mitochondrial network dynamics and autophagic removal of damaged mitochondria. In addition, mitochondrial reactive oxygen species production has been suggested to regulate skeletal muscle insulin sensitivity, which may also be influenced by PGC-1α. This review aims to highlight the current evidence for PGC-1α-mediated regulation of skeletal muscle mitochondrial function beyond the effects on mitochondrial biogenesis as well as the potential PGC-1α-related impact on insulin-stimulated glucose uptake in skeletal muscle. Novelty PGC-1α regulates mitochondrial biogenesis but also has effects on mitochondrial functions beyond biogenesis. Mitochondrial quality control mechanisms, including fission, fusion, and mitophagy, are regulated by PGC-1α. PGC-1α-mediated regulation of mitochondrial quality may affect age-related mitochondrial dysfunction and insulin sensitivity.

scholarly journals Endurance training remodels skeletal muscle phospholipid composition and increases intrinsic mitochondrial respiration in men with Type 2 diabetes

2019 ◽  
Vol 51 (11) ◽  
pp. 586-595 ◽  
Author(s):  
Maria F. Pino ◽  
Natalie A. Stephens ◽  
Alexey M. Eroshkin ◽  
Fanchao Yi ◽  
Andrew Hodges ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Endurance Training ◽  
Mitochondrial Function ◽  
Mitochondrial Respiration ◽  
Phospholipid Composition ◽  
Rna Seq ◽  
Mitochondrial Dna Copy Number

The effects of exercise training on the skeletal muscle (SKM) lipidome and mitochondrial function have not been thoroughly explored in individuals with Type 2 diabetes (T2D). We hypothesize that 10 wk of supervised endurance training improves SKM mitochondrial function and insulin sensitivity that are related to alterations in lipid signatures within SKM of T2D (males n = 8). We employed integrated multi-omics data analyses including ex vivo lipidomics (MS/MS-shotgun) and transcriptomics (RNA-Seq). From biopsies of SKM, tissue and primary myotubes mitochondrial respiration were quantified by high-resolution respirometry. We also performed hyperinsulinemic-euglycemic clamps and blood draws before and after the training. The lipidomics analysis revealed that endurance training (>95% compliance) increased monolysocardiolipin by 68.2% ( P ≤ 0.03), a putative marker of mitochondrial remodeling, and reduced total sphingomyelin by 44.8% ( P ≤ 0.05) and phosphatidylserine by 39.7% ( P ≤ 0.04) and tended to reduce ceramide lipid content by 19.8%. Endurance training also improved intrinsic mitochondrial respiration in SKM of T2D without alterations in mitochondrial DNA copy number or cardiolipin content. RNA-Seq revealed 71 transcripts in SKM of T2D that were differentially regulated. Insulin sensitivity was unaffected, and HbA1c levels moderately increased by 7.3% despite an improvement in cardiorespiratory fitness (V̇o2peak) following the training intervention. In summary, endurance training improves intrinsic and cell-autonomous SKM mitochondrial function and modifies lipid composition in men with T2D independently of alterations in insulin sensitivity and glycemic control.

scholarly journals Impact of aging and exercise on skeletal muscle mitochondrial capacity, energy metabolism, and physical function

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
L. Grevendonk ◽  
N. J. Connell ◽  
C. McCrum ◽  
C. E. Fealy ◽  
L. Bilet ◽  
...  
Keyword(s):  
Physical Activity ◽  
Older Adults ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Mitochondrial Function ◽  
Physical Activity Level ◽  
Activity Level ◽  
Muscle Physiology ◽  
Activity Levels ◽  
Mitochondrial Capacity

AbstractThe relationship between the age-associated decline in mitochondrial function and its effect on skeletal muscle physiology and function remain unclear. In the current study, we examined to what extent physical activity contributes to the decline in mitochondrial function and muscle health during aging and compared mitochondrial function in young and older adults, with similar habitual physical activity levels. We also studied exercise-trained older adults and physically impaired older adults. Aging was associated with a decline in mitochondrial capacity, exercise capacity and efficiency, gait stability, muscle function, and insulin sensitivity, even when maintaining an adequate daily physical activity level. Our data also suggest that a further increase in physical activity level, achieved through regular exercise training, can largely negate the effects of aging. Finally, mitochondrial capacity correlated with exercise efficiency and insulin sensitivity. Together, our data support a link between mitochondrial function and age-associated deterioration of skeletal muscle.

Nitric Oxide Increases Insulin Sensitivity in Skeletal Muscle by Improving Mitochondrial Function and Insulin Signaling

2009 ◽  
Vol 33 (3) ◽  
pp. 198 ◽  
Author(s):  
Woo Je Lee ◽  
Hyoun Sik Kim ◽  
Hye-Sun Park ◽  
Mi-Ok Kim ◽  
Mina Kim ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Mitochondrial Function ◽  
Insulin Signaling

scholarly journals Age, Obesity, and Sex Effects on Insulin Sensitivity and Skeletal Muscle Mitochondrial Function

Diabetes ◽  
2009 ◽  
Vol 59 (1) ◽  
pp. 89-97 ◽  
Author(s):  
H. Karakelides ◽  
B. A. Irving ◽  
K. R. Short ◽  
P. O'Brien ◽  
K. S. Nair
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Mitochondrial Function ◽  
Sex Effects

scholarly journals Skeletal muscle mitochondrial function in polycystic ovarian syndrome

2011 ◽  
Vol 165 (4) ◽  
pp. 631-637 ◽  
Author(s):  
Rasmus Rabøl ◽  
Pernille F Svendsen ◽  
Mette Skovbro ◽  
Robert Boushel ◽  
Peter Schjerling ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
High Resolution ◽  
Mitochondrial Function ◽  
Mitochondrial Respiration ◽  
Complex I ◽  
Polycystic Ovarian Syndrome ◽  
Obese Women ◽  
Mitochondrial Content ◽  
Ovarian Syndrome

ObjectivePolycystic ovarian syndrome (PCOS) is associated with skeletal muscle insulin resistance (IR), which has been linked to decreased mitochondrial function. We measured mitochondrial respiration in lean and obese women with and without PCOS using high-resolution respirometry.MethodsHyperinsulinemic–euglycemic clamps (40 mU/min per m2) and muscle biopsies were performed on 23 women with PCOS (nine lean (body mass index (BMI) <25 kg/m2) and 14 obese (BMI >25 kg/m2)) and 17 age- and weight-matched controls (six lean and 11 obese). Western blotting and high-resolution respirometry was used to determine mitochondrial function.ResultsInsulin sensitivity decreased with PCOS and increasing body weight. Mitochondrial respiration with substrates for complex I and complex I+II were similar in all groups, and PCOS was not associated with a decrease in mitochondrial content as measured by mitochondrial DNA/genomic DNA. We found no correlation between mitochondrial function and indices of insulin sensitivity.ConclusionsIn contrast to previous reports, we found no evidence that skeletal muscle mitochondrial respiration is reduced in skeletal muscle of women with PCOS compared with control subjects. Furthermore, mitochondrial content did not differ between our control and PCOS groups. These results question the causal relationship between reduced mitochondrial function and skeletal muscle IR in PCOS.

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