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This study verified NAFLD pathogenesis via mitochondrial functions in hepatic pathological abnormalities, liver index and weight, body weight, serum biochemical indexes, oxidative stress indicators, mitochondrial function indexes, and related signaling pathways. The effect of fenofibrate intervention was investigated in NAFLD model mice. In vitro, four groups based on HepG2 cells were generated, including controls, the FFA model (1.5 mmol\/L FFA incubation for 24\u00a0h), LV-PGC-1\u03b1 intervention (similar to the FFA model one after PPARGC1A lentivirus transfection), and LV control intervention (similar to the FFA model one after negative control lentivirus transfection) groups. The study investigated the mechanism of PGC-1\u03b1 related to lipid decomposition and mitochondrial biosynthesis by Oil red O staining, colorimetry and western blot.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In vivo experiments, a high-fat diet achieved remarkable changes regarding liver weight, liver index, serum biochemical indicators, oxidative stress indicators, liver pathological changes, mitochondrial function indicators, and body weight of the NAFLD model mice while fenofibrate improved the objective indicators. In the HepG2 cells model, the lipid accumulation increased significantly within the FFA model group, together with aggravated hepatocytic damage and boosted oxidative stress levels. Moreover, FFA induced excessive mitosis into fragmented in mitochondrial morphology, ATP content in cells decreased, mtDNA replication fold decreased, the expression of lipid decomposition protein PPAR\u03b1 reduced, mitochondrial biosynthesis related protein PGC-1\u03b1, NRF-1 and TFAM decreased. PGC-1\u03b1 overexpression inhibited lipid deposition by improving mitochondrial biosynthesis and lipid decomposition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Fenofibrate up-regulated PPAR\u03b1\/PGC-1\u03b1 signaling pathway, promoted mitochondrial \u03b2-oxidation, reduced oxidative stress damage and lipid accumulation of liver. PGC-1\u03b1 overexpression enhanced mitochondrial biosynthesis and ATP production, and reduced HepG2 intracellular accumulation of lipids and oxidative stress.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40360-023-00730-6","type":"journal-article","created":{"date-parts":[[2024,1,3]],"date-time":"2024-01-03T14:03:33Z","timestamp":1704290613000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Fenofibrate alleviates NAFLD by enhancing the PPAR\u03b1\/PGC-1\u03b1 signaling pathway coupling mitochondrial function"],"prefix":"10.1186","volume":"25","author":[{"given":"Xuemei","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cao","family":"Ying","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Men","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,3]]},"reference":[{"key":"730_CR1","doi-asserted-by":"crossref","unstructured":"Dorairaj V, Sulaiman SA, Abu N, Abdul Murad NA. 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