ArticleHepatology (Baltimore, Md.)2021
17-Beta Hydroxysteroid Dehydrogenase 13 Deficiency Does Not Protect Mice From Obesogenic Diet Injury.
Article in Hepatology (Baltimore, Md.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 61 citations in OpenAlex.
- Hepatic Lipoprotein Production, Cardiometabolic Phenotypes, and Subtypes of Steatotic Liver Disease.Circulation research · 2026Review
- Reduction in Hepatic Phosphatidylcholine Biosynthesis Promotes MASH Through Copper Deficiency.bioRxiv : the preprint server for biology · 2026Article
- Metabolic dysfunction-associated steatotic liver disease and steatohepatitis-associated hepatocarcinoma preclinical models.Nature reviews. Gastroenterology & hepatology · 2026Review
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- HSD17β11 regulates PLIN5-ATGL mediated lipolysis, but not hepatic lipid metabolism in mice.Journal of lipid research · 2025Article
- An ethanol-induced loss of the lipid droplet-associated segregase VCP/p97 leads to hepatic steatosis.The Journal of cell biology · 2025Article
- Hydroxysteroid 17β-dehydrogenase 13 (Hsd17b13) knockdown attenuates liver steatosis in high-fat diet obese mice.Experimental physiology · 2025Article
- Gene-based therapies for steatotic liver disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Lipidomic Profiling Reveals HSD17B13 Deficiency-Associated Dysregulated Hepatic Phospholipid Metabolism in Aged Mice.Metabolites · 2025Article
- Therapeutic Targets and Approaches to Manage Inflammation of NAFLD.Biomedicines · 2025Review
- Genetic insights into alcohol-associated liver disease: integrative transcriptome-wide analysis identifies novel susceptibility genes.Frontiers in medicine · 2025Article
- Rab2A-mediated Golgi-lipid droplet interactions support very-low-density lipoprotein secretion in hepatocytes.The EMBO journal · 2024Article
- HSD17B13 liquid-liquid phase separation promotes leukocyte adhesion in chronic liver inflammation.Journal of molecular cell biology · 2024Article
- GCKIII kinases control hepatocellular lipid homeostasis via shared mode of action.Journal of lipid research · 2024Article
- Divergent role of Mitochondrial Amidoxime Reducing Component 1 (MARC1) in human and mouse.PLoS genetics · 2024Article
- Review
- Article
- Unraveling the pathogenesis of non-alcoholic fatty liver diseases through genome-wide association studies.Journal of gastroenterology and hepatology · 2023Review
- Structural basis of lipid-droplet localization of 17-beta-hydroxysteroid dehydrogenase 13.Nature communications · 2023Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
BACKGROUND AND
aims17-Beta hydroxysteroid dehydrogenase 13 (HSD17B13) is genetically associated with human nonalcoholic fatty liver disease (NAFLD). Inactivating mutations in HSD17B13 protect humans from NAFLD-associated and alcohol-associated liver injury, fibrosis, cirrhosis, and hepatocellular carcinoma, leading to clinical trials of anti-HSD17B13 therapeutic agents in humans. We aimed to study the in vivo function of HSD17B13 using a mouse model. APPROACH AND
resultsSingle-cell RNA-sequencing and quantitative RT-PCR data revealed that hepatocytes are the main HSD17B13-expressing cells in mice and humans. We compared Hsd17b13 whole-body knockout (KO) mice and wild-type (WT) littermate controls fed regular chow (RC), a high-fat diet (HFD), a Western diet (WD), or the National Institute on Alcohol Abuse and Alcoholism model of alcohol exposure. HFD and WD induced significant weight gain, hepatic steatosis, and inflammation. However, there was no difference between genotypes with regard to body weight, liver weight, hepatic triglycerides (TG), histological inflammatory scores, expression of inflammation-related and fibrosis-related genes, and hepatic retinoid levels. Compared to WT, KO mice on the HFD had hepatic enrichment of most cholesterol esters, monoglycerides, and certain sphingolipid species. Extended feeding with the WD for 10 months led to extensive liver injury, fibrosis, and hepatocellular carcinoma, with no difference between genotypes. Under alcohol exposure, KO and WT mice showed similar hepatic TG and liver enzyme levels. Interestingly, chow-fed KO mice showed significantly higher body and liver weights compared to WT mice, while KO mice on obesogenic diets had a shift toward larger lipid droplets.
conclusionsExtensive evaluation of Hsd17b13 deficiency in mice under several fatty liver-inducing dietary conditions did not reproduce the protective role of HSD17B13 loss-of-function mutants in human NAFLD. Moreover, mouse Hsd17b13 deficiency induces weight gain under RC. It is crucial to understand interspecies differences prior to leveraging HSD17B13 therapies.
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