ArticleThe Journal of clinical investigation2017
Targeting PPARγ in the epigenome rescues genetic metabolic defects in mice.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 54 citations in OpenAlex.
- A Sensitive Reporter Mouse Model to Study Adipocyte-Derived Extracellular Vesicles In Vivo.Journal of extracellular vesicles · 2026Article
- Transcriptional control of brown adipocyte differentiation and function by NFIA: recent perspectives on deciphering metabolic diseases.Journal of biochemistry · 2025Review
- Adipocyte CLDN5 promotes thermogenesis and energy expenditure through regulation of IL10 expression.Nature communications · 2025Article
- Distinct Roles of Common Genetic Variants and Their Contributions to Diabetes: MODY and Uncontrolled T2DM.Biomolecules · 2025Review
- PPARγ-dependent remodeling of translational machinery in adipose progenitors is impaired in obesity.Cell reports · 2024Article
- Rosiglitazone-induced PPARγ activation promotes intramuscular adipocyte adipogenesis of pig.Animal biotechnology · 2023Article
- Identifying G protein-coupled receptors involved in adipose tissue function using the innovative RNA-seq database FATTLAS.iScience · 2023Article
- Differential Strain-dependent Ovarian and Metabolic Responses in a Mouse Model of PCOS.Endocrinology · 2023Article
- Adipocyte-derived lactate is a signalling metabolite that potentiates adipose macrophage inflammation via targeting PHD2.Nature communications · 2022Article
- NFIA determines theiScience · 2022Article
- Isoform-specific functions of PPARγ in gene regulation and metabolism.Genes & development · 2022Article
- Article
- Study on the role and mechanism of lncRNA in the remodeling of atrial energy metabolism in rabbits with atrial fibrillation based on nano sensor technology.Bioengineered · 2022Article
- Characterization of anNutrients · 2021Article
- Genetic controls of Tas1r3-independent sucrose consumption in mice.Mammalian genome : official journal of the International Mammalian Genome Society · 2021Article
- Genetics of mouse behavioral and peripheral neural responses to sucrose.Mammalian genome : official journal of the International Mammalian Genome Society · 2021Article
- Adipocytes fail to maintain cellular identity during obesity due to reduced PPARγ activity and elevated TGFβ-SMAD signaling.Molecular metabolism · 2020Article
- Article
- Positive Reinforcing Mechanisms between GPR120 and PPARγ Modulate Insulin Sensitivity.Cell metabolism · 2020Article
- Mechanisms of insulin resistance related to white, beige, and brown adipocytes.Molecular metabolism · 2020Review
Corrections and comments
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Authors and funding
21 authors at 2 institutions in 3 countries.
Funding
Abstract
Obesity causes insulin resistance, and PPARγ ligands such as rosiglitazone are insulin sensitizing, yet the mechanisms remain unclear. In C57BL/6 (B6) mice, obesity induced by a high-fat diet (HFD) has major effects on visceral epididymal adipose tissue (eWAT). Here, we report that HFD-induced obesity in B6 mice also altered the activity of gene regulatory elements and genome-wide occupancy of PPARγ. Rosiglitazone treatment restored insulin sensitivity in obese B6 mice, yet, surprisingly, had little effect on gene expression in eWAT. However, in subcutaneous inguinal fat (iWAT), rosiglitazone markedly induced molecular signatures of brown fat, including the key thermogenic gene Ucp1. Obesity-resistant 129S1/SvImJ mice (129 mice) displayed iWAT browning, even in the absence of rosiglitazone. The 129 Ucp1 locus had increased PPARγ binding and gene expression that were preserved in the iWAT of B6x129 F1-intercrossed mice, with an imbalance favoring the 129-derived alleles, demonstrating a cis-acting genetic difference. Thus, B6 mice have genetically defective Ucp1 expression in iWAT. However, when Ucp1 was activated by rosiglitazone, or by iWAT browning in cold-exposed or young mice, expression of the B6 version of Ucp1 was no longer defective relative to the 129 version, indicating epigenomic rescue. These results provide a framework for understanding how environmental influences like drugs can affect the epigenome and potentially rescue genetically determined disease phenotypes.
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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.