ArticlePharmacogenetics and genomics2012
Improved insulin sensitivity after treatment with PPARγ and PPARα ligands is mediated by genetically modulated transcripts.
Article in Pharmacogenetics and genomics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- Metabolic Inflexibility with Obesity and the Effects of Fenofibrate on Skeletal Muscle Fatty Acid Oxidation.Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme · 2017Trial
- Metabolic and Signaling Dysregulation in a Cellular Model of Hepatic Insulin Resistance.Current issues in molecular biology · 2026Article
- The pan-PPAR agonist lanifibranor improves cardiometabolic health in patients with metabolic dysfunction-associated steatohepatitis.Nature communications · 2024Article
- Whole-body insulin resistance and energy expenditure indices, serum lipids, and skeletal muscle metabolome in a state of lipoprotein lipase overexpression.Metabolomics : Official journal of the Metabolomic Society · 2021Article
- Review
- Rosiglitazone remodels the lipid droplet and britens human visceral and subcutaneous adipocytes ex vivo.Journal of lipid research · 2019Article
- Diabetes pharmacotherapy and effects on the musculoskeletal system.Diabetes/metabolism research and reviews · 2019Review
- Modulation of PPAR Expression and Activity in Response to Polyphenolic Compounds in High Fat Diets.International journal of molecular sciences · 2016Review
- Obesity Associated Modulation of miRNA and Co-Regulated Target Transcripts in Human Adipose Tissue of Non-Diabetic Subjects.MicroRNA (Shariqah, United Arab Emirates) · 2015Article
- Expression quantitative trait analyses to identify causal genetic variants for type 2 diabetes susceptibility.World journal of diabetes · 2014Review
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Corrections and comments
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Authors and funding
5 authors at 2 institutions in 3 countries.
Funding
Abstract
objectivesWe aimed to define the effects of peroxisomal proliferator-activated receptor γ (PPARγ) and PPARα agonist mono and combination therapy on adipose tissue and skeletal muscle gene expression in relation to insulin sensitivity. We further investigated the role of genetic polymorphisms in PPAR ligand-modulated genes in transcriptional regulation and glucose homeostasis. MATERIALS AND
methodsGenome-wide transcript profiles of subcutaneous adipose and skeletal muscle and metabolic phenotypes were assessed before and after 10 weeks of pioglitazone and fenofibrate mono or combination therapy in 26 patients with impaired glucose tolerance. To establish the functional role of single nucleotide polymorphisms (SNPs) in genes modulated by pioglitazone alone or in combination with fenofibrate, we examined genome-wide association data of continuous glycemic phenotypes from the Meta-Analyses of Glucose and Insulin-Related Traits Consortium study and adipose eQTL data from the Multi Tissue Human Expression Resource study.
resultsPPARγ, alone or in combination with PPARα agonists, mediated upregulation of genes involved in the TCA cycle, branched-chain amino acid (BCAA) metabolism, fatty acid metabolism, PPAR signaling, AMPK and cAMP signaling, and insulin signaling pathways, and downregulation of genes in antigen processing and presentation, and immune and inflammatory response in adipose tissue. Remarkably few changes were found in muscle. Strong enrichment of genes involved in propanoate metabolism, fatty acid elongation in the mitochondria, and acetyl-CoA metabolic process were observed only in adipose tissue of the combined pioglitazone and fenofibrate treatment group. After examining Meta-Analyses of Glucose and Insulin-Related Traits Consortium data, SNPs in 22 genes modulated by PPAR ligands were associated with fasting plasma glucose and the expression of 28 transcripts modulated by PPAR ligands was under control of local genetic regulators (cis-eQTLs) in adipose tissue of Multi Tissue Human Expression Resource study twins.
conclusionWe found differences in transcriptional mechanisms that may describe the insulin-sensitizing effects of PPARγ agonist monotherapy or in combination with a PPARα agonist. The regulatory and glucose homeostasis trait-associated SNPs in PPAR agonist-modulated genes are important candidates for future studies that may explain the interindividual variability in response to thiazolidinedione and fenofibrate treatment.
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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.