{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T11:02:40Z","timestamp":1785322960605,"version":"3.55.0"},"reference-count":41,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hong Kong Research Grant Committee","award":["CRF\/C5016-23GF"],"award-info":[{"award-number":["CRF\/C5016-23GF"]}]},{"name":"Hong Kong Research Grant Committee","award":["AoE\/M-402\/25-N"],"award-info":[{"award-number":["AoE\/M-402\/25-N"]}]},{"name":"Hong Kong Research Grant Committee","award":["RIF\/R4005-18F"],"award-info":[{"award-number":["RIF\/R4005-18F"]}]},{"name":"GDSTC fund","award":["2025A0505000064"],"award-info":[{"award-number":["2025A0505000064"]}]},{"name":"1+1+1 Joint Collaboration Fund","award":["YSP09"],"award-info":[{"award-number":["YSP09"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>An abnormality of Ca2+ signaling may aggravate lipid accumulation in steatotic hepatocytes, leading to non-alcoholic fatty liver disease. However, the molecular identity of Ca2+-permeable channels and the mechanism of involvement of these channels in steatotic hepatocytes are not well-studied. In the present study, we investigated the role of a Ca2+-permeable channel TRPM2 in lipid metabolism in steatotic hepatocytes. A mouse model of non-alcoholic fatty liver disease was established by high-fat-diet feeding. Fat accumulation, fibrosis, lipophagic indexes, TFEB and lysosomal acid lipase in the liver tissue and\/or hepatocytes were compared between TRPM2-knockout mice and wild-type mice. Knockout of the TRPM2 gene aggravated liver fat accumulation and fibrosis. Mechanistically, the TRPM2 knockout impaired the lipophagic process, decreased lysosomal abundance and attenuated lysosomal\/autolysosomal acidification in mouse hepatocytes. Furthermore, the TRPM2 knockout reduced TFEB expression and its nuclear translation and also reduced the expression\/activity of lysosomal acid lipase. These data demonstrate that TRPM2 deficiency may reduce lipophagy via its action on TFEB and lysosomal acid lipase, consequently contributing to liver steatosis and NAFLD under high-fat feeding conditions.<\/jats:p>","DOI":"10.3390\/cells15151361","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T15:57:28Z","timestamp":1785254248000},"page":"1361","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["TRPM2 Promotes Lipophagy Through TFEB and LAL in HFD-Fed Mice"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0044-6750","authenticated-orcid":false,"given":"Fan","family":"Ying","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"Heart and Vascular Institute and Li Ka Shing Institute of Health Science, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duan","family":"Zhuo","sequence":"additional","affiliation":[{"name":"Southern University of Science and Technology Yantian Hospital, Shenzhen 518081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaobo","family":"Zhou","sequence":"additional","affiliation":[{"name":"Southern University of Science and Technology Yantian Hospital, Shenzhen 518081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7829-1472","authenticated-orcid":false,"given":"Liwen","family":"Jiang","sequence":"additional","affiliation":[{"name":"Centre for Cell and Developmental Biology, State Key Laboratory of Agrobiotechnology, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0687-8186","authenticated-orcid":false,"given":"Xiaoqiang","family":"Yao","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"Heart and Vascular Institute and Li Ka Shing Institute of Health Science, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"Centre for Cell and Developmental Biology, State Key Laboratory of Agrobiotechnology, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1016\/j.cell.2021.04.015","article-title":"Mechanisms and disease consequences of nonalcoholic fatty liver disease","volume":"184","author":"Loomba","year":"2021","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Pouwels, S., Sakran, N., Graham, Y., Leal, A., Pintar, T., Yang, W., Kassir, R., Singhal, R., Mahawar, K., and Ramnarain, D. 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