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Thus, this study aimed to elucidate mechanism of mitochondria mediating HFD-induced hepatic fat accumulation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>In the present study, yellow catfish were fed three diets with dietary fat at 6.31% (low fat; LFD, control), 12.03% (middle fat; MFD) and 15.32% (high fat; HFD), respectively, for 8\u00a0weeks. High dietary fat addition raised hepatic lipid accumulation, and declined mRNA and protein levels of Parkin-dependent mitophagy, down-regulated the Parkin protein expression and the estrogen-related receptor alpha (Err\u03b1) ubiquitination, and induced Err\u03b1 protein levels; fatty acid (FA) incubation reduced Parkin-dependent mitophagy, inhibited Err\u03b1 ubiquitination and increased Err\u03b1 protein expression, and raised TG accumulation. Furthermore, yellow catfish hepatocytes were isolated and cultured. Nicotinamide mononucleotide, <jats:italic>N<\/jats:italic>-acetyl-L-cysteine, Parkin and <jats:italic>err\u03b1<\/jats:italic> siRNA knockdown were used under FA incubation, respectively. Parkin downregulation mediated FA incubation-induced TG accumulation and mitoautophagic inhibition; Parkin ubiquitinated Err\u03b1, and K63 was an important ubiquitination site for deubiquitinating Parkin activity; Err\u03b1 targets <jats:italic>fas<\/jats:italic>, <jats:italic>acca<\/jats:italic> and <jats:italic>ppar\u03b3<\/jats:italic> genes, whose activation contributed to FA-induced lipogenesis and lipid accumulation. Thus, high fat diet (HFD) and FA incubation inhibited Parkin activity, suppressed mitophagy and activated Err\u03b1 pathway, and induced hepatic lipogenic metabolism and lipotoxicity.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Overall, our study provided new targets against HFD-induced hepatic lipid accumulation and non-alcoholic fatty liver disease in the vertebrates.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s40104-025-01200-1","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T23:02:27Z","timestamp":1747782147000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["High fat diet (HFD) induced hepatic lipogenic metabolism and lipotoxicity via Parkin-dependent mitophagy and Err\u03b1 signal of Pelteobagrus fulvidraco"],"prefix":"10.1186","volume":"16","author":[{"given":"Angen","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwei","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ester","family":"Zito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3219-1609","authenticated-orcid":false,"given":"Zhi","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,21]]},"reference":[{"key":"1200_CR1","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/s41575-020-00406-0","volume":"18","author":"MF Abdelmalek","year":"2021","unstructured":"Abdelmalek MF. 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