{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:52:51Z","timestamp":1792623171451,"version":"4.5.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T00:00:00Z","timestamp":1679011200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/ http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>NAFLD has become the leading cause of chronic liver disease worldwide afflicting about one quarter of the adult population. NASH is a severe subtype of NAFLD, which in addition to hepatic steatosis connotes liver inflammation and hepatocyte ballooning. In light of the exponentially increasing prevalence of NAFLD, it is imperative to gain a better understanding of its molecular pathogenesis. The aim of this study was to examine the potential role of STE20-type kinase TAOK1 \u2014a hepatocellular lipid droplet-associated protein\u2014in the regulation of liver lipotoxicity and NAFLD etiology.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>The correlation between <jats:italic toggle=\"yes\">TAOK1<\/jats:italic> mRNA expression in liver biopsies and the severity of NAFLD was evaluated in a cohort of 62 participants. Immunofluorescence microscopy was applied to describe the subcellular localization of TAOK1 in human and mouse hepatocytes. Metabolic reprogramming and oxidative\/endoplasmic reticulum stress were investigated in immortalized human hepatocytes, where TAOK1 was overexpressed or silenced by small interfering RNA, using functional assays, immunofluorescence microscopy, and colorimetric analysis. Migration, invasion, and epithelial-mesenchymal transition were examined in TAOK1-deficient human hepatoma-derived cells. Alterations in hepatocellular metabolic and pro-oncogenic signaling pathways were assessed by immunoblotting.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>We observed a positive correlation between the TAOK1 mRNA abundance in human liver biopsies and key hallmarks of NAFLD (<jats:italic toggle=\"yes\">i.e.<\/jats:italic>, hepatic steatosis, inflammation, and ballooning). Furthermore, we found that TAOK1 protein fully colocalized with intracellular lipid droplets in human and mouse hepatocytes. The silencing of TAOK1 alleviated lipotoxicity in cultured human hepatocytes by accelerating lipid catabolism (mitochondrial \u03b2-oxidation and triacylglycerol secretion), suppressing lipid anabolism (fatty acid influx and lipogenesis), and mitigating oxidative\/endoplasmic reticulum stress, and the opposite changes were detected in TAOK1-overexpressing cells. We also found decreased proliferative, migratory, and invasive capacity, as well as lower epithelial-mesenchymal transition in TAOK1-deficient human hepatoma-derived cells. Mechanistic studies revealed that TAOK1 knockdown inhibited ERK and JNK activation and repressed acetyl-CoA carboxylase (ACC) protein abundance in human hepatocytes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Together, we provide the first experimental evidence supporting the role of hepatic lipid droplet-decorating kinase TAOK1 in NAFLD development through mediating fatty acid partitioning between anabolic and catabolic pathways, regulating oxidative\/endoplasmic reticulum stress, and modulating metabolic and pro-oncogenic signaling.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/hc9.0000000000000037","type":"journal-article","created":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T21:04:33Z","timestamp":1679087073000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":12,"title":["Silencing of STE20-type kinase TAOK1 confers protection against hepatocellular lipotoxicity through metabolic rewiring"],"prefix":"10.1097","volume":"7","author":[{"given":"Ying","family":"Xia","sequence":"first","affiliation":[{"name":"Department of Chemistry and Molecular Biology, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Andersson","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Molecular Biology, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumit K.","family":"Anand","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Molecular Biology, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmelie","family":"Cansby","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Molecular Biology, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Caputo","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Molecular Biology, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sima","family":"Kumari","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Molecular Biology, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rando","family":"Porosk","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalle","family":"Kilk","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syam","family":"Nair","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Physiology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanns-Ulrich","family":"Marschall","sequence":"additional","affiliation":[{"name":"Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, 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