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However, the precise mechanism remains unclear. Here, we explored how IF reduced hepatic lipid accumulation, inflammation, and fibrosis in mice with MASH. The mice were fed a high-fat diet (HFD) for 30 weeks and either continued on the HFD or were subjected to IF for the final 22 weeks. IF reduced body weight, insulin resistance, and hepatic lipid accumulation in HFD-fed mice. Lipidome analysis revealed that IF modified HFD-induced hepatic lipid composition. In particular, HFD-induced impaired autophagic flux was reversed by IF. The decreased hepatic lysosome-associated membrane protein 1 level in HFD-fed mice was upregulated in HFD+IF-fed mice. However, increased hepatic lysosomal acid lipase protein levels in HFD-fed mice were reduced by IF. IF attenuated HFD-induced hepatic inflammation and galectin-3-positive Kupffer cells. In addition to the increases in hepatic hydroxyproline and lumican levels, lipocalin-2-mediated signaling was reversed in HFD-fed mice by IF. Taken together, our findings indicate that the enhancement of the autophagy\u2013lysosomal pathway may be a critical mechanism of MASH reduction by IF.<\/jats:p>","DOI":"10.3390\/nu15214574","type":"journal-article","created":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T09:27:28Z","timestamp":1698658048000},"page":"4574","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Intermittent Fasting Attenuates Metabolic-Dysfunction-Associated Steatohepatitis by Enhancing the Hepatic Autophagy\u2013Lysosome Pathway"],"prefix":"10.3390","volume":"15","author":[{"given":"Kyung Eun","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Anatomy and Convergence Medical Science, College of Medicine, Institute of Medical Science, Gyeongsang National University, Jinju 52727, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Joo","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Convergence Medical Science, College of Medicine, Institute of Medical Science, Gyeongsang National University, Jinju 52727, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeajin","family":"Ju","sequence":"additional","affiliation":[{"name":"Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, Seoul 03759, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youngae","family":"Jung","sequence":"additional","affiliation":[{"name":"Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, Seoul 03759, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeong Seok","family":"An","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Convergence Medical Science, College of Medicine, Institute of Medical Science, Gyeongsang National University, Jinju 52727, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So Jeong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Convergence Medical Science, College of Medicine, Institute of Medical Science, Gyeongsang National University, Jinju 52727, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Ae","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Convergence Medical Science, College of Medicine, Institute of Medical Science, Gyeongsang National University, Jinju 52727, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaewoong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Convergence Medical Science, College of Medicine, Institute of Medical Science, Gyeongsang National University, Jinju 52727, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geum-Sook","family":"Hwang","sequence":"additional","affiliation":[{"name":"Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, Seoul 03759, Republic of Korea"},{"name":"College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4010-9628","authenticated-orcid":false,"given":"Gu Seob","family":"Roh","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Convergence Medical Science, College of Medicine, Institute of Medical Science, Gyeongsang National University, Jinju 52727, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.jhep.2020.03.039","article-title":"A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement","volume":"73","author":"Eslam","year":"2020","journal-title":"J. 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