ArticleMolecular metabolism2020
Adipocytes fail to maintain cellular identity during obesity due to reduced PPARγ activity and elevated TGFβ-SMAD signaling.
Article in Molecular metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 54 citations in OpenAlex.
- Adipocyte Expression of O-Glycoprotein Procollagen C-Endopeptidase Enhancer Protein 2 (PCPE2): Mechanisms Linking Fibrosis and Beiging of White Adipose Tissue.bioRxiv : the preprint server for biology · 2026Article
- E3 ligase SMURF2 promotes adipogenesis and improves obesity complications by suppressing TGF-β signaling.Journal of lipid research · 2026Article
- Reprogramming in delipidated adipocytes: metabolism, regulation and progress.Cell death discovery · 2026Review
- PDGF signaling regulates the adipocyte-to-fibroblast transition in wound healing.Cell reports · 2026Article
- Serum Response Factor (SRF) promotes actin cytoskeletal organization in adipocytes to support adaptive hypertrophic expansion and tissue remodeling during obesity in mice.Metabolism: clinical and experimental · 2026Article
- Caspase-6 Controls Lipid and Energy Metabolism in Diet-Induced Obesity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- EBF2 variant identified in a patient with atypical partial lipodystrophy causes adipose fibrosis and dysfunction.The Journal of clinical investigation · 2026Article
- How Adipocytes Orchestrate Inflammation Within Adipose Tissue?Biomolecules · 2025Review
- Mirabegron treatment reduces myofibroblasts and CXCR2 expression in adipose tissue in obesity.Molecular medicine (Cambridge, Mass.) · 2025Article
- Unraveling the complexities of diet induced obesity and glucolipid dysfunction in metabolic syndrome.Diabetology & metabolic syndrome · 2025Review
- ECM formation and degradation during fibrosis, repair, and regeneration.npj metabolic health and disease · 2025Review
- Monoclonal antibody therapy for PCOS?Cell metabolism · 2025Article
- Acute regulation of murine adipose tissue lipolysis and insulin resistance by the TGFβ superfamily protein GDF3.Nature communications · 2025Article
- Enhancing adipose tissue plasticity: progenitor cell roles in metabolic health.Nature reviews. Endocrinology · 2025Review
- RBM43 controls PGC1α translation and a PGC1α-STING signaling axis.Cell metabolism · 2025Article
- Neurotensin-neurotensin receptor 2 signaling in adipocytes suppresses food intake through regulating ceramide metabolism.Cell research · 2025Article
- Role of transforming growth factor-β1 in regulating adipocyte progenitors.Scientific reports · 2025Article
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- A molecular mechanism for bright color variation in parrots.Science (New York, N.Y.) · 2024Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveObesity due to overnutrition causes adipose tissue dysfunction, which is a critical pathological step on the road to type 2 diabetes (T2D) and other metabolic disorders. In this study, we conducted an unbiased investigation into the fundamental molecular mechanisms by which adipocytes transition to an unhealthy state during obesity.
methodsWe used nuclear tagging and translating ribosome affinity purification (NuTRAP) reporter mice crossed with Adipoq-Cre mice to determine adipocyte-specific 1) transcriptional profiles (RNA-seq), 2) promoter and enhancer activity (H3K27ac ChIP-seq), 3) and PPARγ cistrome (ChIP-seq) profiles in mice fed chow or a high-fat diet (HFD) for 10 weeks. We also assessed the impact of the PPARγ agonist rosiglitazone (Rosi) on gene expression and cellular state of adipocytes from the HFD-fed mice. We integrated these data to determine the transcription factors underlying adipocyte responses to HFD and conducted functional studies using shRNA-mediated loss-of-function approaches in 3T3-L1 adipocytes.
resultsAdipocytes from the HFD-fed mice exhibited reduced expression of adipocyte markers and metabolic genes and enhanced expression of myofibroblast marker genes involved in cytoskeletal organization, accompanied by the formation of actin filament structures within the cell. PPARγ binding was globally reduced in adipocytes after HFD feeding, and Rosi restored the molecular and cellular phenotypes of adipocytes associated with HFD feeding. We identified the TGFβ1 effector protein SMAD to be enriched at HFD-induced promoters and enhancers and associated with myofibroblast signature genes. TGFβ1 treatment of mature 3T3-L1 adipocytes induced gene expression and cellular changes similar to those seen after HFD in vivo, and knockdown of Smad3 blunted the effects of TGFβ1.
conclusionsOur data demonstrate that adipocytes fail to maintain cellular identity after HFD feeding, acquiring characteristics of a myofibroblast-like cell type through reduced PPARγ activity and elevated TGFβ-SMAD signaling. This cellular identity crisis may be a fundamental mechanism that drives functional decline of adipose tissues during obesity.
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