{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:29:10Z","timestamp":1792290550598,"version":"4.4.0"},"reference-count":51,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T00:00:00Z","timestamp":1716768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Startup Fund for scientific research, Fujian Medical University","award":["2020QH2007"],"award-info":[{"award-number":["2020QH2007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by diffuse hepatocellular steatosis due to fatty deposits in hepatocytes, excluding alcohol and other known liver injury factors. However, there are no specific drugs for the clinical treatment of NAFLD. Therefore, research on the pathogenesis of NAFLD at the cellular and molecular levels is a promising approach to finding therapeutic targets and developing targeted drugs for NAFLD. Pin1 is highly expressed during adipogenesis and contributes to adipose differentiation, but its specific mechanism of action in NAFLD is unclear. In this study, we investigated the role of Pin1 in promoting the development of NAFLD and its potential mechanisms in vitro and in vivo. First, Pin1 was verified in the NAFLD model in vitro using MCD diet-fed mice by Western Blot, RT-qPCR and immunohistochemistry (IHC) assays. In the in vitro study, we used the oleic acid (OA) stimulation-induced lipid accumulation model and examined the lipid accumulation in each group of cells by oil red O staining as well as BODIPY staining. The results showed that knockdown of Pin1 inhibited lipid accumulation in hepatocytes in an in vitro lipid accumulation model and improved lipid indices and liver injury levels. Moreover, in vivo, WT and Pin1-KO mice were fed a methionine-choline deficient (MCD) diet for 4 weeks to induce the NAFLD model. The effects of Pin1 on lipid accumulation, hepatic fibrosis, and oxidative stress were evaluated by biochemical analysis, glucose and insulin tolerance tests, histological analysis, IHC, RT-qPCR and Western blot assays. The results indicate that Pin1 knockdown significantly alleviated hepatic steatosis, fibrosis and inflammation in MCD-induced NAFLD mice, improved glucose tolerance and alleviated insulin resistance in mice. Further studies showed that the AMPK\/ACC1 signalling pathway might take part in the process by which Pin1 regulates NAFLD, as evidenced by the inhibition of the AMPK\/ACC1 pathway. In addition, immunofluorescence (IF), coimmunoprecipitation (Co-IP) and GST pull-down experiments also showed that Pin1 interacts directly with ACC1 and inhibits ACC1 phosphorylation levels. Our study suggests that Pin1 promotes NAFLD progression by inhibiting the activation of the AMPK\/ACC1 signalling pathway, and it is possible that this effect is achieved by Pin1 interacting with ACC1 and inhibiting the phosphorylation of ACC1.<\/jats:p>","DOI":"10.3390\/ijms25115822","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T10:14:07Z","timestamp":1716804847000},"page":"5822","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Pin1 Exacerbates Non-Alcoholic Fatty Liver Disease by Enhancing Its Activity through Binding to ACC1"],"prefix":"10.3390","volume":"25","author":[{"given":"Yiyi","family":"Jin","sequence":"first","affiliation":[{"name":"Fujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, The School of Basic Medical Sciences, Fujian Medical University, No. 1, Xuefu North Road, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoshui","family":"Shangguan","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, The School of Basic Medical Sciences, Fujian Medical University, No. 1, Xuefu North Road, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Pang","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, The School of Basic Medical Sciences, Fujian Medical University, No. 1, Xuefu North Road, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3025-7096","authenticated-orcid":false,"given":"Yuwen","family":"Chen","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, The School of Basic Medical Sciences, Fujian Medical University, No. 1, Xuefu North Road, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suijin","family":"Lin","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, The School of Basic Medical Sciences, Fujian Medical University, No. 1, Xuefu North Road, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hekun","family":"Liu","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, The School of Basic Medical Sciences, Fujian Medical University, No. 1, Xuefu North Road, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1038\/nrgastro.2013.171","article-title":"The global NAFLD epidemic","volume":"10","author":"Loomba","year":"2013","journal-title":"Nat. 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