{"entity": "journal", "iuid": "d8617520c0ab40a4b8e88b85d975d10a", "timestamp": "2026-09-26T23:04:03.943Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/journal/Cell%20Mol%20Gastroenterol%20Hepatol.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/journal/Cell%20Mol%20Gastroenterol%20Hepatol"}}, "title": "Cell Mol Gastroenterol Hepatol", "issn": "2352-345X", "issn-l": null, "publications_count": 1, "publications": [{"entity": "publication", "iuid": "0d0c1931606c44dca8822f11e47eb8f9", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/0d0c1931606c44dca8822f11e47eb8f9.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/0d0c1931606c44dca8822f11e47eb8f9"}}, "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"}, {"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"}, {"family": "Aghajan", "given": "Mariam", "initials": "M"}, {"family": "Mahlapuu", "given": "Margit", "initials": "M"}], "type": "journal article", "published": "2018-12-19", "journal": {"title": "Cell Mol Gastroenterol Hepatol", "issn": "2352-345X", "volume": "7", "issue": "3", "pages": "597-618", "issn-l": null}, "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": [], "xrefs": [{"db": "pmc", "key": "PMC6411916"}, {"db": "pii", "key": "S2352-345X(18)30179-6"}], "notes": [], "created": "2026-09-23T09:26:51.624Z", "modified": "2026-09-23T09:26:51.672Z"}], "created": "2026-09-23T09:26:51.634Z", "modified": "2026-09-23T09:26:51.634Z"}