biostudies-literatureDiaz-Saez FGeneralitat de CatalunyaCIBERDEM Instituto de Salud Carlos IIIFundación Ramón ArecesFundació La Marató de TV3MICINN11718https://www.ebi.ac.uk/biostudies/studies/S-EPMC11546241biostudies-literatureUnknown25(21)Neuregulin 4 (Nrg4) is an adipokine that belongs to the epidermal growth factor family and binds to ErbB4 tyrosine kinase receptors. In 3T3-L1 adipocytes, the downregulation of <i>Nrg4</i> expression enhances inflammation and autophagy, resulting in insulin resistance. Here, we searched for the causes of this phenotype. Nrg4 knockdown (Nrg4 KD) adipocytes showed a significant reduction in mitochondrial content and elongation, along with a lower content of the mitochondria fusion protein mitofusin 2 (MFN2), and increased H₂O₂ production compared to the control scrambled cells (Scr). The antioxidant N-acetylcysteine reversed the oxidative stress and reduced the gene expression of the pro-inflammatory cytokine tumor necrosis factor α (TNFα). Nrg4 KD adipocytes showed enhInternational journal of molecular sciencesNeuregulin 4 Downregulation Alters Mitochondrial Morphology and Induces Oxidative Stress in 3T3-L1 Adipocytes.PMC11546241XX534/C/2016PID2019-106209RB-100201626-30PID2022-137576OB-100CIVP18A3942Camps MBalcells CRicart WDiaz-Saez FRomero MGuma ALopez-Soldado ISebastian DMoreno-Navarrete JMFernandez-Real JMAragones JRossello LZorzano ACascante MBusquets SLopez-Soriano FJTestar XfalseNeuregulin 4 Downregulation Alters Mitochondrial Morphology and Induces Oxidative Stress in 3T3-L1 Adipocytes.Neuregulin 4 (Nrg4) is an adipokine that belongs to the epidermal growth factor family and binds to ErbB4 tyrosine kinase receptors. In 3T3-L1 adipocytes, the downregulation of <i>Nrg4</i> expression enhances inflammation and autophagy, resulting in insulin resistance. Here, we searched for the causes of this phenotype. Nrg4 knockdown (Nrg4 KD) adipocytes showed a significant reduction in mitochondrial content and elongation, along with a lower content of the mitochondria fusion protein mitofusin 2 (MFN2), and increased H₂O₂ production compared to the control scrambled cells (Scr). The antioxidant N-acetylcysteine reversed the oxidative stress and reduced the gene expression of the pro-inflammatory cytokine tumor necrosis factor α (TNFα). Nrg4 KD adipocytes showed enh2024-01-01T00:00:00Z2024 Oct2026-07-12T03:14:02.077Z2025-04-06T01:45:39.689ZS-EPMC115462413951926910.3390/ijms252111718