ArticleDiabetologia2006
Peroxisome proliferator-activated receptor-gamma coactivator-1 and insulin resistance: acute effect of fatty acids.
Article in Diabetologia, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Pooled it
- L-carnitine infusion does not alleviate lipid-induced insulin resistance and metabolic inflexibility.PloS one · 2020Trial
- Evidence for a direct effect of the NAD+ precursor acipimox on muscle mitochondrial function in humans.Diabetes · 2015Trial
- Common variation at PPARGC1A/B and change in body composition and metabolic traits following preventive interventions: the Diabetes Prevention Program.Diabetologia · 2014Trial
- Exercise with low glycogen increases PGC-1α gene expression in human skeletal muscle.European journal of applied physiology · 2013Trial
- Transcriptomic responses to repeated exposure of human C3A liver spheroids to polystyrene nanoplastics.Archives of toxicology · 2026Article
- Comparative transcriptome analysis of pectoralis major muscles affected by white striping, wooden breast and spaghetti meat in male and female broiler chickens.BMC genomics · 2025Article
- Maternal metabolizable energy intake during late gestation affects energy metabolism of the skeletal muscle of beef offspring.Journal of animal science · 2025Article
- The Intersection of Genetic Factors, Aberrant Nutrient Metabolism and Oxidative Stress in the Progression of Cardiometabolic Disease.Antioxidants (Basel, Switzerland) · 2024Review
- Diets Rich in Olive Oil, Palm Oil, or Lard Alter Mitochondrial Biogenesis and Mitochondrial Membrane Composition in Rat Liver.Biochemistry research international · 2022Article
- Mitochondrial Dysfunction and Mitophagy Closely Cooperate in Neurological Deficits Associated with Alzheimer's Disease and Type 2 Diabetes.Molecular neurobiology · 2021Review
- Irisin/FNDC5: A participant in camel metabolism.Saudi journal of biological sciences · 2021Article
- Multi-Tissue DNA Methylation Remodeling at Mitochondrial Quality Control Genes According to Diet in Rat Aging Models.Nutrients · 2020Article
- Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet.Frontiers in physiology · 2019Review
- Mitochondrial dynamics in type 2 diabetes: Pathophysiological implications.Redox biology · 2017Review
- Liver fat: a relevant target for dietary intervention? Summary of a Unilever workshop.Journal of nutritional science · 2017Review
- Lack of UCP3 does not affect skeletal muscle mitochondrial function under lipid-challenged conditions, but leads to sudden cardiac death.Basic research in cardiology · 2014Article
- Influence of fish oil on skeletal muscle mitochondrial energetics and lipid metabolites during high-fat diet.American journal of physiology. Endocrinology and metabolism · 2013Article
- Relationships between mitochondrial function and metabolic flexibility in type 2 diabetes mellitus.PloS one · 2013Article
- Genome-wide association study indicates variants associated with insulin signaling and inflammation mediate lipoprotein responses to fenofibrate.Pharmacogenetics and genomics · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisPeroxisome proliferator-activated receptor (PPAR)-gamma coactivator-1 (PPARGC1), a coactivator regulating the transcription of genes involved in oxidative metabolism, is downregulated in patients with type 2 diabetes and in their first-degree relatives. Whether this downregulation is a cause or effect of early aberrations in the development of insulin resistance, such as disturbances in fat metabolism, is unknown. We examined whether lipid-induced insulin resistance was associated with downregulation of expression of skeletal muscle genes involved in oxidative metabolism and mitochondrial biogenesis in humans. MATERIALS AND
methodsNine healthy lean male subjects underwent a 6-h hyperinsulinaemic-euglycaemic clamp with simultaneous infusion of either a lipid emulsion or glycerol as a control. Blood was sampled at regular time points and muscle biopsies were taken before and after every test. Intramuscular triacylglycerol (IMTG) content was determined by Oil Red O staining and gene expression was measured by quantitative PCR.
resultsLipid infusion resulted in a approximately 2.7-fold increase in plasma NEFA levels and a 31+/-6% decrease in insulin sensitivity (p=0.001). The infusion of lipids resulted in a approximately 1.6-fold increase in IMTG (p=0.02), whereas during the clamp with glycerol infusion IMTG tended to decrease to approximately 53% of preinfusion levels (p=0.065). Lipid infusion decreased PPARGC1A, PPARGC1B and PPARA expression to approximately 61, 77 and approximately 52% of basal values respectively, whereas expression of uncoupling protein 3 was upregulated 1.8-fold (all p<0.05). CONCLUSIONS/
interpretationAcute elevation of plasma NEFA levels, leading to muscular fat accumulation and insulin resistance, downregulates PPARGC1A, PPARGC1B and PPARA expression, suggesting that the decrease in PPARGC1 expression observed in the (pre)diabetic state may be the result, rather than the cause of lipid-induced 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.