{"entity": "researcher", "timestamp": "2026-08-09T08:02:12.103Z", "family": "Marschall", "given": "Hanns Ulrich", "initials": "HU", "orcid": "0000-0001-7347-3085", "affiliations": [], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/82b16fa78a994d12bd49ed280012893c.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/82b16fa78a994d12bd49ed280012893c"}}, "publications": [{"entity": "publication", "iuid": "332a80d7bd944ad0b4a7b3cf05772f55", "links": {"self": {"href": "https://publications.scilifelab.se/publication/332a80d7bd944ad0b4a7b3cf05772f55.json"}, "display": {"href": "https://publications.scilifelab.se/publication/332a80d7bd944ad0b4a7b3cf05772f55"}}, "title": "STE20-type kinases MST3 and MST4 promote the progression of hepatocellular carcinoma: Evidence from human cell culture and expression profiling of liver biopsies.", "authors": [{"family": "Caputo", "given": "Mara", "initials": "M", "orcid": "0000-0002-3362-9062", "researcher": {"href": "https://publications.scilifelab.se/researcher/0996a47cc52e411192c58145efb697a7.json"}}, {"family": "Xia", "given": "Ying", "initials": "Y", "orcid": "0000-0002-8133-5413", "researcher": {"href": "https://publications.scilifelab.se/researcher/76735d31b0fb4707bb43c8e89ba450dc.json"}}, {"family": "Anand", "given": "Sumit Kumar", "initials": "SK", "orcid": "0000-0003-3719-0744", "researcher": {"href": "https://publications.scilifelab.se/researcher/b888c8d483d24dbd893e75dca060c0d5.json"}}, {"family": "Cansby", "given": "Emmelie", "initials": "E", "orcid": "0000-0003-1589-3596", "researcher": {"href": "https://publications.scilifelab.se/researcher/48cf95c633c4424ab268f9ecaa311456.json"}}, {"family": "Andersson", "given": "Emma", "initials": "E", "orcid": "0000-0001-7382-9045", "researcher": {"href": "https://publications.scilifelab.se/researcher/13a36347d64f46ea94571868a9d468c3.json"}}, {"family": "Marschall", "given": "Hanns-Ulrich", "initials": "HU", "orcid": "0000-0001-7347-3085", "researcher": {"href": "https://publications.scilifelab.se/researcher/82b16fa78a994d12bd49ed280012893c.json"}}, {"family": "K\u00f6nigsrainer", "given": "Alfred", "initials": "A", "orcid": "0000-0002-2301-4080", "researcher": {"href": "https://publications.scilifelab.se/researcher/88cce6ee93ce496e982dafc19da1a709.json"}}, {"family": "Peter", "given": "Andreas", "initials": "A", "orcid": "0000-0001-5732-2287", "researcher": {"href": "https://publications.scilifelab.se/researcher/de73c6b72c1045b5bfcb60720d32e714.json"}}, {"family": "Mahlapuu", "given": "Margit", "initials": "M", "orcid": "0000-0001-8740-8874", "researcher": {"href": "https://publications.scilifelab.se/researcher/db46c5dea6e8445888d7cad506d438c8.json"}}], "type": "journal article", "published": "2023-08-00", "journal": {"title": "FASEB J.", "issn": "1530-6860", "volume": "37", "issue": "8", "pages": "e23105", "issn-l": "0892-6638"}, "abstract": "Hepatocellular carcinoma (HCC) is one of the most fatal and fastest growing malignancies. Recently, nonalcoholic steatohepatitis (NASH), characterized by liver steatosis, inflammation, cell injury (hepatocyte ballooning), and different stages of fibrosis, has emerged as a major catalyst for HCC. Because the STE20-type kinases, MST3 and MST4, have been described as critical molecular regulators of NASH pathophysiology, we here focused on determining the relevance of these proteins in human HCC. By analyzing public datasets and in-house cohorts, we found that hepatic MST3 and MST4 expression was positively correlated with the incidence and severity of HCC. We also found that the silencing of both MST3 and MST4, but also either of them individually, markedly suppressed the tumorigenesis of human HCC cells including attenuated proliferation, migration, invasion, and epithelial-mesenchymal transition. Mechanistic investigations revealed lower activation of STAT3 signaling in MST3/MST4-deficient hepatocytes and identified GOLGA2 and STRIPAK complex as the binding partners of both MST3 and MST4. These findings reveal that MST3 and MST4 play a critical role in promoting the progression of HCC and suggest that targeting these kinases may provide a novel strategy for the treatment of liver cancer.", "doi": "10.1096/fj.202300397RR", "pmid": "37490000", "labels": {"Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [], "notes": [], "created": "2023-12-04T10:20:16.325Z", "modified": "2024-01-16T13:46:27.364Z"}, {"entity": "publication", "iuid": "3ff26f3035a34dcf986ff705e9e1a9d5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3ff26f3035a34dcf986ff705e9e1a9d5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3ff26f3035a34dcf986ff705e9e1a9d5"}}, "title": "Absence of gut microbiota reduces neonatal survival and exacerbates liver disease in Cyp2c70-deficient mice with a human-like bile acid composition.", "authors": [{"family": "Sj\u00f6land", "given": "Wilhelm", "initials": "W"}, {"family": "Wahlstr\u00f6m", "given": "Annika", "initials": "A"}, {"family": "Makki", "given": "Kassem", "initials": "K"}, {"family": "Sch\u00f6ler", "given": "Marc", "initials": "M"}, {"family": "Molinaro", "given": "Antonio", "initials": "A"}, {"family": "Olsson", "given": "Lisa", "initials": "L"}, {"family": "Greiner", "given": "Thomas Uwe", "initials": "TU"}, {"family": "Caesar", "given": "Robert", "initials": "R"}, {"family": "de Boer", "given": "Jan Freark", "initials": "JF"}, {"family": "Kuipers", "given": "Folkert", "initials": "F"}, {"family": "B\u00e4ckhed", "given": "Fredrik", "initials": "F"}, {"family": "Marschall", "given": "Hanns-Ulrich", "initials": "HU", "orcid": "0000-0001-7347-3085", "researcher": {"href": "https://publications.scilifelab.se/researcher/82b16fa78a994d12bd49ed280012893c.json"}}], "type": "journal article", "published": "2023-07-14", "journal": {"title": "Clin Sci (Lond)", "issn": "1470-8736", "volume": "137", "issue": "13", "pages": "995-1011", "issn-l": null}, "abstract": "Mice with deletion of Cyp2c70 have a human-like bile acid composition, display age- and sex-dependent signs of hepatobiliary disease and can be used as a model to study interactions between bile acids and the gut microbiota in cholestatic liver disease. In the present study, we rederived Cyp2c70-/- mice as germ-free (GF) and colonized them with a human or a mouse microbiota to investigate whether the presence of a microbiota can be protective in cholangiopathic liver disease associated with Cyp2c70-deficiency. GF Cyp2c70-/- mice showed reduced neonatal survival, liver fibrosis, and distinct cholangiocyte proliferation. Colonization of germ-free breeding pairs with a human or a mouse microbiota normalized neonatal survival of the offspring, and particularly colonization with mouse microbiota from a conventionally raised mouse improved the liver phenotype at 6-10 weeks of age. The improved liver phenotype in conventionalized (CD) Cyp2c70-/- mice was associated with increased levels of tauro-ursodeoxycholic acid (TUDCA) and UDCA, resulting in a more hydrophilic bile acid profile compared with GF and humanized Cyp2c70-/- mice. The hydrophobicity index of biliary bile acids of CD Cyp2c70-/- mice was associated with changes in gut microbiota, liver weight, liver transaminases, and liver fibrosis. Hence, our results indicate that neonatal survival of Cyp2c70-/- mice seems to depend on the establishment of a gut microbiota at birth, and the improved liver phenotype in CD Cyp2c70-/- mice may be mediated by a larger proportion of TUDCA/UDCA in the circulating bile acid pool and/or by the presence of specific bacteria.", "doi": "10.1042/CS20230413", "pmid": "37384590", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10346113"}, {"db": "pii", "key": "233241"}], "notes": [], "created": "2023-11-27T21:50:55.812Z", "modified": "2024-01-16T13:48:32.888Z"}, {"entity": "publication", "iuid": "d6cdaeea853f4ba6ac8a25c2fbc6673e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d6cdaeea853f4ba6ac8a25c2fbc6673e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d6cdaeea853f4ba6ac8a25c2fbc6673e"}}, "title": "6\u03b1-hydroxylated bile acids mediate TGR5 signalling to improve glucose metabolism upon dietary fiber supplementation in mice.", "authors": [{"family": "Makki", "given": "Kassem", "initials": "K"}, {"family": "Brolin", "given": "Harald", "initials": "H"}, {"family": "Petersen", "given": "Natalia", "initials": "N"}, {"family": "Henricsson", "given": "Marcus", "initials": "M"}, {"family": "Christensen", "given": "Dan Ploug", "initials": "DP"}, {"family": "Khan", "given": "Muhammad Tanweer", "initials": "MT"}, {"family": "Wahlstr\u00f6m", "given": "Annika", "initials": "A"}, {"family": "Bergh", "given": "Per-Olof", "initials": "PO"}, {"family": "Tremaroli", "given": "Valentina", "initials": "V"}, {"family": "Schoonjans", "given": "Kristina", "initials": "K"}, {"family": "Marschall", "given": "Hanns-Ulrich", "initials": "HU", "orcid": "0000-0001-7347-3085", "researcher": {"href": "https://publications.scilifelab.se/researcher/82b16fa78a994d12bd49ed280012893c.json"}}, {"family": "B\u00e4ckhed", "given": "Fredrik", "initials": "F", "orcid": "0000-0002-4871-8818", "researcher": {"href": "https://publications.scilifelab.se/researcher/1689878e0c5542d08d3e2d5043a6ce5c.json"}}], "type": "journal article", "published": "2023-02-00", "journal": {"title": "Gut", "issn": "1468-3288", "volume": "72", "issue": "2", "pages": "314-324", "issn-l": "0017-5749"}, "abstract": "Dietary fibres are essential for maintaining microbial diversity and the gut microbiota can modulate host physiology by metabolising the fibres. Here, we investigated whether the soluble dietary fibre oligofructose improves host metabolism by modulating bacterial transformation of secondary bile acids in mice fed western-style diet.\n\nTo assess the impact of dietary fibre supplementation on bile acid transformation by gut bacteria, we fed conventional wild-type and TGR5 knockout mice western-style diet enriched or not with cellulose or oligofructose. In addition, we used germ-free mice and in vitro cultures to evaluate the activity of bacteria to transform bile acids in the caecal content of mice fed with western-style diet enriched with oligofructose. Finally, we treated wild-type and TGR5 knockout mice orally with hyodeoxycholic acid to assess its antidiabetic effects.\n\nWe show that oligofructose sustains the production of 6\u03b1-hydroxylated bile acids from primary bile acids by gut bacteria when fed western-style diet. Mechanistically, we demonstrated that the effects of oligofructose on 6\u03b1-hydroxylated bile acids were microbiota dependent and specifically required functional TGR5 signalling to reduce body weight gain and improve glucose metabolism. Furthermore, we show that the 6\u03b1-hydroxylated bile acid hyodeoxycholic acid stimulates TGR5 signalling, in vitro and in vivo, and increases GLP-1R activity to improve host glucose metabolism.\n\nModulation of the gut microbiota with oligofructose enriches bacteria involved in 6\u03b1-hydroxylated bile acid production and leads to TGR5-GLP1R axis activation to improve body weight and metabolism under western-style diet feeding in mice.", "doi": "10.1136/gutjnl-2021-326541", "pmid": "35697422", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9872241"}, {"db": "pii", "key": "gutjnl-2021-326541"}], "notes": [], "created": "2023-11-27T21:57:42.283Z", "modified": "2024-01-16T13:48:34.074Z"}, {"entity": "publication", "iuid": "ce0f7b27e88b45078db3fbf46d71516b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ce0f7b27e88b45078db3fbf46d71516b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ce0f7b27e88b45078db3fbf46d71516b"}}, "title": "A Fatty Diet Induces a Jejunal Ketogenesis Which Inhibits Local SGLT1-Based Glucose Transport via an Acetylation Mechanism-Results from a Randomized Cross-Over Study between Iso-Caloric High-Fat versus High-Carbohydrate Diets in Healthy Volunteers.", "authors": [{"family": "Elebring", "given": "Erik", "initials": "E"}, {"family": "Wallenius", "given": "Ville", "initials": "V", "orcid": "0000-0001-8668-3196", "researcher": {"href": "https://publications.scilifelab.se/researcher/e728cf3f550046a590066de0e0cd47aa.json"}}, {"family": "Casselbrant", "given": "Anna", "initials": "A", "orcid": "0000-0001-7514-7435", "researcher": {"href": "https://publications.scilifelab.se/researcher/994b2b65cd154b359f5228eb0c69828b.json"}}, {"family": "Docherty", "given": "Neil G", "initials": "NG"}, {"family": "Roux", "given": "Carel W le", "initials": "CWL", "orcid": "0000-0001-5521-5445", "researcher": {"href": "https://publications.scilifelab.se/researcher/3def373e973945889670140361ad8ee5.json"}}, {"family": "Marschall", "given": "Hanns-Ulrich", "initials": "HU", "orcid": "0000-0001-7347-3085", "researcher": {"href": "https://publications.scilifelab.se/researcher/82b16fa78a994d12bd49ed280012893c.json"}}, {"family": "F\u00e4ndriks", "given": "Lars", "initials": "L", "orcid": "0000-0003-0736-3034", "researcher": {"href": "https://publications.scilifelab.se/researcher/32daf05ef1f541cbbdf0b4de2fbd142e.json"}}], "type": "journal article", "published": "2022-05-07", "journal": {"title": "Nutrients", "issn": "2072-6643", "volume": "14", "issue": "9", "issn-l": "2072-6643"}, "abstract": "Insights into the nature of gut adaptation after different diets enhance the understanding of how food modifications can be used to treat type 2 diabetes and obesity. The aim was to understand how diets, enriched in fat or carbohydrates, affect glucose absorption in the human healthy jejunum, and what mechanisms are involved.\n\nFifteen healthy subjects received, in randomised order and a crossover study design, two weeks of iso-caloric high-fat diet (HFD) and high-carbohydrate diet (HCD). Following each dietary period, jejunal mucosa samples were retrieved and assessed for protein expression using immunofluorescence and western blotting. Functional characterisation of epithelial glucose transport was assessed ex vivo using Ussing chambers. Regulation of SGLT1 through histone acetylation was studied in vitro in Caco-2 and human jejunal enteroid monolayer cultures.\n\nHFD, compared to HCD, decreased jejunal Ussing chamber epithelial glucose transport and the expression of apical transporters for glucose (SGLT1) and fructose (GLUT5), while expression of the basolateral glucose transporter GLUT2 was increased. HFD also increased protein expression of the ketogenesis rate-limiting enzyme mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) and decreased the acetylation of histone 3 at lysine 9 (H3K9ac). Studies in Caco-2 and human jejunal enteroid monolayer cultures indicated a ketogenesis-induced activation of sirtuins, in turn decreasing SGLT1 expression.\n\nJejunal glucose absorption is decreased by a fat-enriched diet, via a ketogenesis-induced alteration of histone acetylation responsible for the silencing of SGLT1 transcription. The work relates to a secondary outcome in ClinicalTrials.gov (NCT02088853).", "doi": "10.3390/nu14091961", "pmid": "35565929", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9100393"}, {"db": "pii", "key": "nu14091961"}, {"db": "ClinicalTrials.gov", "key": "NCT02088853"}], "notes": [], "created": "2023-02-16T08:23:40.094Z", "modified": "2023-02-16T08:23:40.167Z"}, {"entity": "publication", "iuid": "18226df579c94c61955019463d361b96", "links": {"self": {"href": "https://publications.scilifelab.se/publication/18226df579c94c61955019463d361b96.json"}, "display": {"href": "https://publications.scilifelab.se/publication/18226df579c94c61955019463d361b96"}}, "title": "Silencing of STE20-type kinase STK25 in human aortic endothelial and smooth muscle cells is atheroprotective.", "authors": [{"family": "Cansby", "given": "Emmelie", "initials": "E", "orcid": "0000-0003-1589-3596", "researcher": {"href": "https://publications.scilifelab.se/researcher/48cf95c633c4424ab268f9ecaa311456.json"}}, {"family": "Kumari", "given": "Sima", "initials": "S"}, {"family": "Caputo", "given": "Mara", "initials": "M"}, {"family": "Xia", "given": "Ying", "initials": "Y"}, {"family": "Porosk", "given": "Rando", "initials": "R"}, {"family": "Robinson", "given": "Jonathan", "initials": "J"}, {"family": "Wang", "given": "Hao", "initials": "H", "orcid": "0000-0001-7475-0136", "researcher": {"href": "https://publications.scilifelab.se/researcher/836b4fbf7ebd4f80abc84465c8f29a2e.json"}}, {"family": "Olsson", "given": "Britt-Marie", "initials": "BM"}, {"family": "Vallin", "given": "Josefine", "initials": "J"}, {"family": "Grantham", "given": "Julie", "initials": "J"}, {"family": "Soomets", "given": "Ursel", "initials": "U", "orcid": "0000-0002-3681-188X", "researcher": {"href": "https://publications.scilifelab.se/researcher/72cc178012864ea5a642a15ca1bb6a19.json"}}, {"family": "Svensson", "given": "L Thomas", "initials": "LT"}, {"family": "Sihlbom", "given": "Carina", "initials": "C"}, {"family": "Marschall", "given": "Hanns-Ulrich", "initials": "HU", "orcid": "0000-0001-7347-3085", "researcher": {"href": "https://publications.scilifelab.se/researcher/82b16fa78a994d12bd49ed280012893c.json"}}, {"family": "Edsfeldt", "given": "Andreas", "initials": "A"}, {"family": "Goncalves", "given": "Isabel", "initials": "I"}, {"family": "Mahlapuu", "given": "Margit", "initials": "M", "orcid": "0000-0001-8740-8874", "researcher": {"href": "https://publications.scilifelab.se/researcher/db46c5dea6e8445888d7cad506d438c8.json"}}], "type": "journal article", "published": "2022-04-19", "journal": {"title": "Commun Biol", "issn": "2399-3642", "issn-l": "2399-3642", "volume": "5", "issue": "1", "pages": "379"}, "abstract": "Recent studies highlight the importance of lipotoxic damage in aortic cells as the major pathogenetic contributor to atherosclerotic disease. Since the STE20-type kinase STK25 has been shown to exacerbate ectopic lipid storage and associated cell injury in several metabolic organs, we here investigate its role in the main cell types of vasculature. We depleted STK25 by small interfering RNA in human aortic endothelial and smooth muscle cells exposed to oleic acid and oxidized LDL. In both cell types, the silencing of STK25 reduces lipid accumulation and suppresses activation of inflammatory and fibrotic pathways as well as lowering oxidative and endoplasmic reticulum stress. Notably, in smooth muscle cells, STK25 inactivation hinders the shift from a contractile to a synthetic phenotype. Together, we provide several lines of evidence that antagonizing STK25 signaling in human aortic endothelial and smooth muscle cells is atheroprotective, highlighting this kinase as a new potential therapeutic target for atherosclerotic disease.", "doi": "10.1038/s42003-022-03309-9", "pmid": "35440683", "labels": {"Systems Biology": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "Glycoproteomics and MS Proteomics": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC9018782"}, {"db": "pii", "key": "10.1038/s42003-022-03309-9"}], "notes": [], "created": "2022-11-10T17:22:43.040Z", "modified": "2024-01-16T13:46:29.345Z"}, {"entity": "publication", "iuid": "25cc25920817401d9ee280754cef42da", "links": {"self": {"href": "https://publications.scilifelab.se/publication/25cc25920817401d9ee280754cef42da.json"}, "display": {"href": "https://publications.scilifelab.se/publication/25cc25920817401d9ee280754cef42da"}}, "title": "Glycemic Control and Metabolic Adaptation in Response to High-Fat versus High-Carbohydrate Diets-Data from a Randomized Cross-Over Study in Healthy Subjects.", "authors": [{"family": "Wallenius", "given": "Ville", "initials": "V", "orcid": "0000-0001-8668-3196", "researcher": {"href": "https://publications.scilifelab.se/researcher/e728cf3f550046a590066de0e0cd47aa.json"}}, {"family": "Elebring", "given": "Erik", "initials": "E"}, {"family": "Casselbrant", "given": "Anna", "initials": "A", "orcid": "0000-0001-7514-7435", "researcher": {"href": "https://publications.scilifelab.se/researcher/994b2b65cd154b359f5228eb0c69828b.json"}}, {"family": "Laurenius", "given": "Anna", "initials": "A", "orcid": "0000-0002-9150-1876", "researcher": {"href": "https://publications.scilifelab.se/researcher/26456e3b48e648749dd6353200c225bf.json"}}, {"family": "le Roux", "given": "Carel W", "initials": "CW"}, {"family": "Docherty", "given": "Neil G", "initials": "NG"}, {"family": "Bi\u00f6rserud", "given": "Christina", "initials": "C"}, {"family": "Bj\u00f6rnfot", "given": "Niclas", "initials": "N"}, {"family": "Engstr\u00f6m", "given": "My", "initials": "M", "orcid": "0000-0002-4616-468X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3157542f861e40ba87731e9dd112be04.json"}}, {"family": "Marschall", "given": "Hanns-Ulrich", "initials": "HU", "orcid": "0000-0001-7347-3085", "researcher": {"href": "https://publications.scilifelab.se/researcher/82b16fa78a994d12bd49ed280012893c.json"}}, {"family": "F\u00e4ndriks", "given": "Lars", "initials": "L", "orcid": "0000-0003-0736-3034", "researcher": {"href": "https://publications.scilifelab.se/researcher/32daf05ef1f541cbbdf0b4de2fbd142e.json"}}], "type": "journal article", "published": "2021-09-23", "journal": {"title": "Nutrients", "issn": "2072-6643", "volume": "13", "issue": "10", "issn-l": "2072-6643"}, "abstract": "Granular study of metabolic responses to alterations in the ratio of dietary macro-nutrients can enhance our understanding of how dietary modifications influence patients with impaired glycemic control. In order to study the effect of diets enriched in fat or carbohydrates, fifteen healthy, normal-weight volunteers received, in a cross-over design, and in a randomized unblinded order, two weeks of an iso-caloric high-fat diet (HFD: 60E% from fat) and a high-carbohydrate diet (HCD: 60E% from carbohydrates). A mixed meal test (MMT) was performed at the end of each dietary period to examine glucose clearance kinetics and insulin and incretin hormone levels, as well as plasma metabolomic profiles. The MMT induced almost identical glycemia and insulinemia following the HFD or HCD. GLP-1 levels were higher after the HFD vs. HCD, whereas GIP did not differ. The HFD, compared to the HCD, increased the levels of several metabolomic markers of risk for the development of insulin resistance, e.g., branched-chain amino acid (valine and leucine), creatine and \u03b1-hydroxybutyric acid levels. In normal-weight, healthy volunteers, two weeks of the HFD vs. HCD showed similar profiles of meal-induced glycemia and insulinemia. Despite this, the HFD showed a metabolomic pattern implying a risk for a metabolic shift towards impaired insulin sensitivity in the long run.", "doi": "10.3390/nu13103322", "pmid": "34684324", "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [{"db": "pii", "key": "nu13103322"}, {"db": "pmc", "key": "PMC8538379"}], "notes": [], "created": "2021-12-08T15:46:09.857Z", "modified": "2025-10-17T13:03:55.570Z"}, {"entity": "publication", "iuid": "bac285d364884f36a578d224961ce13e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bac285d364884f36a578d224961ce13e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bac285d364884f36a578d224961ce13e"}}, "title": "Targeted Delivery of Stk25 Antisense Oligonucleotides to Hepatocytes Protects Mice Against Nonalcoholic Fatty Liver Disease.", "authors": [{"family": "Cansby", "given": "Emmelie", "initials": "E"}, {"family": "Nu\u00f1ez-Dur\u00e1n", "given": "Esther", "initials": "E"}, {"family": "Magnusson", "given": "Elin", "initials": "E"}, {"family": "Amrutkar", "given": "Manoj", "initials": "M", "orcid": "0000-0002-1868-0249", "researcher": {"href": "https://publications.scilifelab.se/researcher/b36803e9b38d49b797904ae896f4c8b9.json"}}, {"family": "Booten", "given": "Sheri L", "initials": "SL"}, {"family": "Kulkarni", "given": "Nagaraj M", "initials": "NM"}, {"family": "Svensson", "given": "L Thomas", "initials": "LT"}, {"family": "Bor\u00e9n", "given": "Jan", "initials": "J"}, {"family": "Marschall", "given": "Hanns-Ulrich", "initials": "HU", "orcid": "0000-0001-7347-3085", "researcher": {"href": "https://publications.scilifelab.se/researcher/82b16fa78a994d12bd49ed280012893c.json"}}, {"family": "Aghajan", "given": "Mariam", "initials": "M"}, {"family": "Mahlapuu", "given": "Margit", "initials": "M"}], "type": "journal article", "published": "2018-12-19", "journal": {"volume": "7", "issn": "2352-345X", "issue": "3", "pages": "597-618", "title": "Cellular and Molecular Gastroenterology and Hepatology", "issn-l": "2352-345X"}, "abstract": "Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are emerging as leading causes of liver disease worldwide. Currently, no specific pharmacologic therapy is available for NAFLD/NASH, which has been recognized as one of the major unmet medical needs of the 21st century. Our recent studies in genetic mouse models, human cell lines, and well-characterized patient cohorts have identified serine/threonine protein kinase (STK)25 as a critical regulator of hepatic lipid partitioning and NAFLD/NASH. Here, we studied the metabolic benefit of liver-specific STK25 inhibitors on NAFLD development and progression in a mouse model of diet-induced obesity.\n\nWe developed a hepatocyte-specific triantennary N-acetylgalactosamine (GalNAc)-conjugated antisense oligonucleotide (ASO) targeting Stk25 and evaluated its effect on NAFLD features in mice after chronic exposure to dietary lipids.\n\nWe found that systemic administration of hepatocyte-targeting GalNAc-Stk25 ASO in obese mice effectively ameliorated steatosis, inflammatory infiltration, hepatic stellate cell activation, nutritional fibrosis, and hepatocellular damage in the liver compared with mice treated with GalNAc-conjugated nontargeting ASO, without any systemic toxicity or local tolerability concerns. We also observed protection against high-fat-diet-induced hepatic oxidative stress and improved mitochondrial function with Stk25 ASO treatment in mice. Moreover, GalNAc-Stk25 ASO suppressed lipogenic gene expression and acetyl-CoA carboxylase protein abundance in the liver, providing insight into the molecular mechanisms underlying repression of hepatic steatosis.\n\nThis study provides in vivo nonclinical proof-of-principle for the metabolic benefit of liver-specific inhibition of STK25 in the context of obesity and warrants future investigations to address the therapeutic potential of GalNAc-Stk25 ASO in the prevention and treatment of NAFLD.", "doi": "10.1016/j.jcmgh.2018.12.004", "pmid": "30576769", "labels": {"Systems Biology": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S2352-345X(18)30179-6"}, {"db": "pmc", "key": "PMC6411916"}], "notes": [], "created": "2020-01-07T14:36:35.939Z", "modified": "2021-06-21T13:47:37.099Z"}]}