ArticleDiabetologia2016
ANT1-mediated fatty acid-induced uncoupling as a target for improving myocellular insulin sensitivity.
Article in Diabetologia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Differences in Mitochondrial Coupling Reveal a Novel Signature of Mitohormesis in Muscle of Healthy Individuals.The Journal of clinical endocrinology and metabolism · 2016Trial
- SLC25A4Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Fatty acids promote uncoupled respiration via ATP/ADP carriers in white adipocytes.Nature metabolism · 2026Article
- Mild Mitochondrial Uncoupling for True Ectopic Lipid Disposal.International journal of molecular sciences · 2025Review
- The effects of major abdominal surgery on skeletal muscle mitochondrial respiration in relation to systemic redox status and cardiopulmonary fitness.Experimental biology and medicine (Maywood, N.J.) · 2025Article
- Deletion of miPEP in adipocytes protects against obesity and insulin resistance by boosting muscle metabolism.Molecular metabolism · 2024Article
- BAM15 as a mitochondrial uncoupler: a promising therapeutic agent for diverse diseases.Frontiers in endocrinology · 2023Review
- Cortisol Regulates Cerebral Mitochondrial Oxidative Phosphorylation and Morphology of the Brain in a Region-Specific Manner in the Ovine Fetus.Biomolecules · 2022Article
- Glucocorticoid maturation of mitochondrial respiratory capacity in skeletal muscle before birth.The Journal of endocrinology · 2021Article
- Effect of heat acclimation on metabolic adaptations induced by endurance training in soleus rat muscle.Physiological reports · 2021Article
- High metabolic substrate load induces mitochondrial dysfunction in rat skeletal muscle microvascular endothelial cells.Physiological reports · 2021Article
- Diabetes Mellitus, Mitochondrial Dysfunction and CaInternational journal of molecular sciences · 2020Review
- Proinflammatory NFkB signalling promotes mitochondrial dysfunction in skeletal muscle in response to cellular fuel overloading.Cellular and molecular life sciences : CMLS · 2019Article
- Quantification of Mitochondrial Oxidative Phosphorylation in Metabolic Disease: Application to Type 2 Diabetes.International journal of molecular sciences · 2019Review
- Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases.Cells · 2019Review
- Skeletal muscle performance in metabolic disease: Microvascular or mitochondrial limitation or both?Microcirculation (New York, N.Y. : 1994) · 2019Review
- Protein assemblies ejected directly from native membranes yield complexes for mass spectrometry.Science (New York, N.Y.) · 2018Article
- The manifold role of the mitochondria in skeletal muscle insulin resistance.Current opinion in clinical nutrition and metabolic care · 2018Review
- Targeting thermogenesis in brown fat and muscle to treat obesity and metabolic disease.Nature reviews. Endocrinology · 2018Review
- Combatting type 2 diabetes by turning up the heat.Diabetologia · 2016Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisDissipating energy via mitochondrial uncoupling has been suggested to contribute to enhanced insulin sensitivity. We hypothesised that skeletal muscle mitochondria of endurance-trained athletes have increased sensitivity for fatty acid (FA)-induced uncoupling, which is driven by the mitochondrial protein adenine nucleotide translocase 1 (ANT1).
methodsCapacity for FA-induced uncoupling was measured in endurance-trained male athletes (T) and sedentary young men (UT) in an observational study and also in isolated skeletal muscle mitochondria from Zucker diabetic fatty (ZDF) rats and C2C12 myotubes following small interfering RNA (siRNA)-mediated gene silencing of ANT1. Thus, fuelled by glutamate/succinate (fibres) or pyruvate (mitochondria and myotubes) and in the presence of oligomycin to block ATP synthesis, increasing levels of oleate (fibres) or palmitate (mitochondria and myotubes) were automatically titrated while respiration was monitored. Insulin sensitivity was measured by hyperinsulinaemic-euglycaemic clamp in humans and via insulin-stimulated glucose uptake in myotubes.
resultsSkeletal muscle from the T group displayed increased sensitivity to FA-induced uncoupling (p = 0.011) compared with muscle from the UT group, and this was associated with elevated insulin sensitivity (p = 0.034). ANT1 expression was increased in T (p = 0.013). Mitochondria from ZDF rats displayed decreased sensitivity for FA-induced uncoupling (p = 0.008). This difference disappeared in the presence of the adenine nucleotide translocator inhibitor carboxyatractyloside. Partial knockdown of ANT1 in C2C12 myotubes decreased sensitivity to the FA-induced uncoupling (p = 0.008) and insulin-stimulated glucose uptake (p = 0.025) compared with controls. CONCLUSIONS/
interpretationIncreased sensitivity to FA-induced uncoupling is associated with enhanced insulin sensitivity and is affected by ANT1 activity in skeletal muscle. FA-induced mitochondrial uncoupling may help to preserve insulin sensitivity in the face of a high supply of FAs.
trial registrationwww.trialregister.nl NTR2002.
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