Hydroxysteroid (17β) dehydrogenase 13 deficiency triggers hepatic steatosis and inflammation in mice.
| Title: | Hydroxysteroid (17β) dehydrogenase 13 deficiency triggers hepatic steatosis and inflammation in mice. |
|---|---|
| Authors: | Adam M; Research Centre for Integrative Physiology and Pharmacology, Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, Turku, Finland.; Heikelä H; Research Centre for Integrative Physiology and Pharmacology, Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, Turku, Finland.; Sobolewski C; Department of Cell Physiology and Metabolism, Faculty of Medicine, Centre Médical Universitaire, Geneva, Switzerland.; Portius D; Department of Cell Physiology and Metabolism, Faculty of Medicine, Centre Médical Universitaire, Geneva, Switzerland.; Mäki-Jouppila J; Research Centre for Integrative Physiology and Pharmacology, Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, Turku, Finland.; Mehmood A; Research Centre for Integrative Physiology and Pharmacology, Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, Turku, Finland.; Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland.; Adhikari P; Research Centre for Integrative Physiology and Pharmacology, Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, Turku, Finland.; Esposito I; Institute of Pathology, Technische Universität München, Munich, Germany; and.; Elo LL; Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland.; Zhang FP; Research Centre for Integrative Physiology and Pharmacology, Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, Turku, Finland.; Ruohonen ST; Research Centre for Integrative Physiology and Pharmacology, Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, Turku, Finland.; Strauss L; Research Centre for Integrative Physiology and Pharmacology, Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, Turku, Finland.; Foti M; Department of Cell Physiology and Metabolism, Faculty of Medicine, Centre Médical Universitaire, Geneva, Switzerland.; Poutanen M; Research Centre for Integrative Physiology and Pharmacology, Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, Turku, Finland.; Department of Internal Medicine, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. |
| Source: | FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2018 Jun; Vol. 32 (6), pp. 3434-3447. Date of Electronic Publication: 2018 Jan 31. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Federation of American Societies for Experimental Biology Country of Publication: United States NLM ID: 8804484 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1530-6860 (Electronic) Linking ISSN: 08926638 NLM ISO Abbreviation: FASEB J Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2020- : [Bethesda, Md.] : Hoboken, NJ : Federation of American Societies for Experimental Biology ; Wiley; Original Publication: [Bethesda, Md.] : The Federation, [c1987- |
| MeSH Terms: | Lipid Metabolism*; 17-Hydroxysteroid Dehydrogenases/*deficiency ; Fatty Liver/*enzymology; Acetyl-CoA Carboxylase/genetics ; Acetyl-CoA Carboxylase/metabolism ; Fatty Acid Synthase, Type I/genetics ; Fatty Acid Synthase, Type I/metabolism ; Fatty Liver/genetics ; Fatty Liver/pathology ; Glucose-6-Phosphatase/genetics ; Glucose-6-Phosphatase/metabolism ; Inflammation/enzymology ; Inflammation/genetics ; Inflammation/pathology ; Mitochondria, Liver/enzymology ; Mitochondria, Liver/genetics ; Mitochondria, Liver/pathology ; Stearoyl-CoA Desaturase/genetics ; Stearoyl-CoA Desaturase/metabolism ; Animals ; Mice ; Mice, Knockout ; Oxidation-Reduction |
| Abstract: | Hydroxysteroid (17β) dehydrogenases (HSD17Bs) form an enzyme family characterized by their ability to catalyze reactions in steroid and lipid metabolism. In the present study, we characterized the phenotype of HSD17B13-knockout (HSD17B13KO) mice deficient in Hsd17b13. In these studies, hepatic steatosis was detected in HSD17B13KO male mice, indicated by histologic analysis and by the increased triglyceride concentration in the liver, whereas reproductive performance and serum steroid concentrations were normal in HSD17B13KO mice. In line with these changes, the expression of key proteins in fatty acid synthesis, such as FAS, acetyl-CoA carboxylase 1, and SCD1, was increased in the HSD17B13KO liver. Furthermore, the knockout liver showed an increase in 2 acylcarnitines, suggesting impaired mitochondrial β-oxidation in the presence of unaltered malonyl CoA and AMPK expression. The glucose tolerance did not differ between wild-type and HSD17B13KO mice in the presence of lower levels of glucose 6-phosphatase in HSD17B13KO liver compared with wild-type liver. Furthermore, microgranulomas and increased portal inflammation together with up-regulation of immune response genes were observed in HSD17B13KO mice. Our data indicate that disruption of Hsd17b13 impairs hepatic-lipid metabolism in mice, resulting in liver steatosis and inflammation, but the enzyme does not play a major role in the regulation of reproductive functions.-Adam, M., Heikelä, H., Sobolewski, C., Portius, D., Mäki-Jouppila, J., Mehmood, A., Adhikari, P., Esposito, I., Elo, L. L., Zhang, F.-P., Ruohonen, S. T., Strauss, L., Foti, M., Poutanen, M. Hydroxysteroid (17β) dehydrogenase 13 deficiency triggers hepatic steatosis and inflammation in mice. |
| Contributed Indexing: | Keywords: lipid droplet; liver; steatohepatitis |
| Substance Nomenclature: | EC 1.1.- (17-Hydroxysteroid Dehydrogenases); EC 1.1.- (17beta-hydroxysteroid dehydrogenase type 13, mouse); EC 1.14.19.1 (Scd1 protein, mouse); EC 1.14.19.1 (Stearoyl-CoA Desaturase); EC 2.3.1.85 (Fatty Acid Synthase, Type I); EC 3.1.3.9 (Glucose-6-Phosphatase); EC 6.4.1.2 (ACC1 protein, mouse); EC 6.4.1.2 (Acetyl-CoA Carboxylase) |
| Entry Date(s): | Date Created: 20180207 Date Completed: 20190115 Latest Revision: 20190115 |
| Update Code: | 20260130 |
| DOI: | 10.1096/fj.201700914R |
| PMID: | 29401633 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't