ArticleProceedings of the National Academy of Sciences of the United States of America2008
Paradoxical effects of increased expression of PGC-1alpha on muscle mitochondrial function and insulin-stimulated muscle glucose metabolism.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 163 papers.
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Who cites it
163 citing papers in PubMed, 277 citations in OpenAlex.
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- Reversal of muscle insulin resistance by weight reduction in young, lean, insulin-resistant offspring of parents with type 2 diabetes.Proceedings of the National Academy of Sciences of the United States of America · 2012 · on this mapTrial
- Effect of short-term free Fatty acids elevation on mitochondrial function in skeletal muscle of healthy individuals.The Journal of clinical endocrinology and metabolism · 2010Trial
- Irisin as an Exerkine of Neuroprotection in Aging and Alzheimer's Disease.Biomolecules · 2026Review
- Intermittent AP-1 activation in muscles contributes to exercise-induced health benefits.bioRxiv : the preprint server for biology · 2026Article
- PGC-1α: a potential therapeutic target for upper airway dilator muscle structure and dysfunction in OSA.Sleep & breathing = Schlaf & Atmung · 2025Review
- Skeletal Muscle PGC-1α Remodels Mitochondrial Phospholipidome but Does Not Alter Energy Efficiency for ATP Synthesis.Journal of cachexia, sarcopenia and muscle · 2025Article
- Sex-specific metabolic responses to high-fat diet in mice with NOX4 deficiency.Redox biology · 2025Article
- Tribbles 3 blunts exercise-induced skeletal muscle adaptation.bioRxiv : the preprint server for biology · 2025Article
- The Hydrophilic Metabolite UMP Alleviates Obesity Traits through a HIF2α-ACER2-Ceramide Signaling Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Alterations in Skeletal Muscle Insulin Signaling DNA Methylation: A Pilot Randomized Controlled Trial of Olanzapine in Healthy Volunteers.Biomedicines · 2024Article
- Skeletal muscle TET3 promotes insulin resistance through destabilisation of PGC-1α.Diabetologia · 2024Article
- Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases.Signal transduction and targeted therapy · 2024Review
- Review
- CDK4-E2F3 signals enhance oxidative skeletal muscle fiber numbers and function to affect myogenesis and metabolism.The Journal of clinical investigation · 2023Article
- PGC-1α Is a Master Regulator of Mitochondrial Lifecycle and ROS Stress Response.Antioxidants (Basel, Switzerland) · 2023Review
- Endurance exercise under short-duration intermittent hypoxia promotes endurance performance via improving muscle metabolic properties in mice.Physiological reports · 2022Article
- Estrogen-related receptor alpha is an AMPK-regulated factor that promotes ischemic muscle revascularization and recovery in diet-induced obese mice.FASEB bioAdvances · 2022Article
- Adipocyte-Specific Expression of PGC1α Promotes Adipocyte Browning and Alleviates Obesity-Induced Metabolic Dysfunction in an HO-1-Dependent Fashion.Antioxidants (Basel, Switzerland) · 2022Article
- Sirt6 reprograms myofibers to oxidative type through CREB-dependent Sox6 suppression.Nature communications · 2022Article
103 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
Peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha has been shown to play critical roles in regulating mitochondria biogenesis, respiration, and muscle oxidative phenotype. Furthermore, reductions in the expression of PGC-1alpha in muscle have been implicated in the pathogenesis of type 2 diabetes. To determine the effect of increased muscle-specific PGC-1alpha expression on muscle mitochondrial function and glucose and lipid metabolism in vivo, we examined body composition, energy balance, and liver and muscle insulin sensitivity by hyperinsulinemic-euglycemic clamp studies and muscle energetics by using (31)P magnetic resonance spectroscopy in transgenic mice. Increased expression of PGC-1alpha in muscle resulted in a 2.4-fold increase in mitochondrial density, which was associated with an approximately 60% increase in the unidirectional rate of ATP synthesis. Surprisingly, there was no effect of increased muscle PGC-1alpha expression on whole-body energy expenditure, and PGC-1alpha transgenic mice were more prone to fat-induced insulin resistance because of decreased insulin-stimulated muscle glucose uptake. The reduced insulin-stimulated muscle glucose uptake could most likely be attributed to a relative increase in fatty acid delivery/triglyceride reesterfication, as reflected by increased expression of CD36, acyl-CoA:diacylglycerol acyltransferase1, and mitochondrial acyl-CoA:glycerol-sn-3-phosphate acyltransferase, that may have exceeded mitochondrial fatty acid oxidation, resulting in increased intracellular lipid accumulation and an increase in the membrane to cytosol diacylglycerol content. This, in turn, caused activation of PKC, decreased insulin signaling at the level of insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation, and skeletal muscle insulin resistance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.