ArticleJournal of cellular and molecular medicine2018
NEFA-induced ROS impaired insulin signalling through the JNK and p38MAPK pathways in non-alcoholic steatohepatitis.
Article in Journal of cellular and molecular medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 87 citations in OpenAlex.
- Neuregulin 4 in Insulin Resistance: Mechanisms, Controversies, and Therapeutic Perspectives.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Docosahexaenoic acid (DHA) alleviates hepatic lipid deposition in dairy cows during the transition period: an integrated in vitro and in vivo study.Journal of animal science and biotechnology · 2025Article
- Protective effects of S-adenosyl methionine on oxidative stress and tissue damage in STZ-induced diabetic rats.Amino acids · 2025Article
- TIMM8B promotes oxidative phosphorylation and glycolysis by inhibiting the mtROS/ASK1/JNK signaling pathway in ovarian cancer.Biology direct · 2025Article
- The In Vitro Effects of Choline on Non-Esterified Fatty Acid-Treated Bovine Peripheral Blood Leukocytes.Animals : an open access journal from MDPI · 2025Article
- Isorhamnetin Ameliorates Non-Esterified Fatty Acid-Induced Apoptosis, Lipid Accumulation, and Oxidative Stress in Bovine Endometrial Epithelial Cells via Inhibiting the MAPK Signaling Pathway.Antioxidants (Basel, Switzerland) · 2025Article
- The role of mitochondria-associated ER membranes in disease pathology: protein complex and therapeutic targets.Frontiers in cell and developmental biology · 2025Review
- Correlation of non-esterified fatty acids with acute coronary syndrome risk in young Chinese adults.Frontiers in endocrinology · 2025Article
- Article
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- Metabolomic analysis of rumen-protected branched-chain amino acids in primiparous dairy cows.Frontiers in immunology · 2024Article
- Role of transcription factor FOXM1 in diabetes and its complications (Review).International journal of molecular medicine · 2023Article
- Mitochondrial dynamics in health and disease: mechanisms and potential targets.Signal transduction and targeted therapy · 2023Review
- Reactive Oxygen Species: A Crosslink between Plant and Human Eukaryotic Cell Systems.International journal of molecular sciences · 2023Review
- Mitofusin-2 gene polymorphisms and metabolic dysfunction associated fatty liver disease: a case-control study in a Chinese population.The Journal of international medical research · 2023Article
- Puerarin Alleviates HInternational journal of molecular sciences · 2023Article
- Astragaloside IV ameliorates insulin induced insulin resistance in HepG2 cells through reactive oxygen species mediated c-Jun N-terminal kinase pathway.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2023Article
- CSAD Ameliorates Lipid Accumulation in High-Fat Diet-Fed Mice.International journal of molecular sciences · 2022Article
- Liraglutide Regulates Mitochondrial Quality Control System Through PGC-1α in a Mouse Model of Parkinson's Disease.Neurotoxicity research · 2022Article
- Effects of supplementation of sodium acetate on rumen fermentation and microbiota in postpartum dairy cows.Frontiers in microbiology · 2022Article
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Authors and funding
9 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
The aim of this study was to investigate the changes in hepatic oxidative phosphorylation (OXPHOS) complexes (COs) in patients and cows with non-alcoholic steatohepatitis (NASH) and to investigate the mechanism that links mitochondrial dysfunction and hepatic insulin resistance induced by non-esterified fatty acids (NEFAs). Patients and cows with NASH displayed high blood NEFAs, TNF-α and IL-6 concentrations, mitochondrial dysfunction and insulin resistance. The protein levels of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), mitofusin-2 (Mfn-2) and OXPHOS complexes (human: COI and COIII; cow: COI-IV) were significantly decreased in patients and cows with NASH. NEFA treatment significantly impaired mitochondrial function and, increased reactive oxygen species (ROS) production, and excessive ROS overactivated the JNK and p38MAPK pathways and induced insulin resistance in cow hepatocytes. PGC-1α and Mfn-2 overexpression significantly decreased the NEFA-induced ROS production and TNF-α and IL-6 mRNA expressions, reversed the inhibitory effect of NEFAs on mitochondrial function and attenuated the overactivation of the ROS-JNK/p38MAPK pathway, alleviated insulin resistance induced by NEFAs in cow hepatocytes and HepG2 cells. These findings indicate that NEFAs induce mitochondrial dysfunction and insulin resistance mediated by the ROS-JNK/p38MAPK pathway. PGC-1α or Mfn-2 overexpression reversed the lipotoxicity of NEFAs on mitochondrial dysfunction and insulin resistance. Our study clarified the mechanism that links hepatic mitochondrial dysfunction and insulin resistance in NASH.
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