biostudies-literatureCataldi SEuropean Foundation for the Study of DiabetesMinistero dell’Istruzione, dell’Università e della Ricerca42https://www.ebi.ac.uk/biostudies/studies/S-EPMC8750445biostudies-literatureUnknown11(1)Low-grade chronic inflammation and reduced differentiation capacity are hallmarks of hypertrophic adipose tissue (AT) and key contributors of insulin resistance. We identified PPARGΔ5 as a dominant-negative splicing isoform overexpressed in the AT of obese/diabetic patients able to impair adipocyte differentiation and PPARγ activity in hypertrophic adipocytes. Herein, we investigate the impact of macrophage-secreted pro-inflammatory factors on PPARG splicing, focusing on PPARGΔ5. We report that the epididymal AT of LPS-treated mice displays increased PpargΔ5/cPparg ratio and reduced expression of Pparg-regulated genes. Interestingly, pro-inflammatory factors secreted from murine and human pro-inflammatory macrophages enhance the PPARGΔ5/cPPARG ratio in exposed adipogenic precursors. TNFα iCellsTNFα Mediates Inflammation-Induced Effects on PPARG Splicing in Adipose Tissue and Mesenchymal Precursor Cells.PMC8750445Boehringer Ingelheim European Research Programme in Microvascular Complications of DiabetesPON Ricerca e Innovazione 2014–2020, PON Ars01_01270 “Innovative Device For SHAping the Risk of Diabetes” (IDF SHARID)Melillo DTanti JFMucel IItaliani PAprile MCormont MBluher MCosta VCataldi SCiccodicola AGiorgetti-Peraldi SfalseTNFα Mediates Inflammation-Induced Effects on PPARG Splicing in Adipose Tissue and Mesenchymal Precursor Cells.Low-grade chronic inflammation and reduced differentiation capacity are hallmarks of hypertrophic adipose tissue (AT) and key contributors of insulin resistance. We identified PPARGΔ5 as a dominant-negative splicing isoform overexpressed in the AT of obese/diabetic patients able to impair adipocyte differentiation and PPARγ activity in hypertrophic adipocytes. Herein, we investigate the impact of macrophage-secreted pro-inflammatory factors on PPARG splicing, focusing on PPARGΔ5. We report that the epididymal AT of LPS-treated mice displays increased PpargΔ5/cPparg ratio and reduced expression of Pparg-regulated genes. Interestingly, pro-inflammatory factors secreted from murine and human pro-inflammatory macrophages enhance the PPARGΔ5/cPPARG ratio in exposed adipogenic precursors. TNFα i2021-01-01T00:00:00Z2021 Dec2025-06-01T12:06:37.386Z2025-06-01T12:06:37.386ZS-EPMC87504453501160410.3390/cells11010042