Hydroxysteroid (17β) dehydrogenase 13 deficiency triggers hepatic steatosis and inflammation in mice
- PMID: 29401633
- DOI: 10.1096/fj.201700914R
Hydroxysteroid (17β) dehydrogenase 13 deficiency triggers hepatic steatosis and inflammation in mice
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.
Keywords: lipid droplet; liver; steatohepatitis.
Similar articles
-
Chronic administration of recombinant IL-6 upregulates lipogenic enzyme expression and aggravates high-fat-diet-induced steatosis in IL-6-deficient mice.Dis Model Mech. 2015 Jul 1;8(7):721-31. doi: 10.1242/dmm.019166. Epub 2015 May 14. Dis Model Mech. 2015. PMID: 26035386 Free PMC article.
-
Methionine restriction prevents the progression of hepatic steatosis in leptin-deficient obese mice.Metabolism. 2013 Nov;62(11):1651-61. doi: 10.1016/j.metabol.2013.06.012. Epub 2013 Aug 5. Metabolism. 2013. PMID: 23928105
-
Tangshen formula attenuates hepatic steatosis by inhibiting hepatic lipogenesis and augmenting fatty acid oxidation in db/db mice.Int J Mol Med. 2016 Dec;38(6):1715-1726. doi: 10.3892/ijmm.2016.2799. Epub 2016 Nov 10. Int J Mol Med. 2016. PMID: 27840945 Free PMC article.
-
Role of HSD17B13 in the liver physiology and pathophysiology.Mol Cell Endocrinol. 2019 Jun 1;489:119-125. doi: 10.1016/j.mce.2018.10.014. Epub 2018 Oct 24. Mol Cell Endocrinol. 2019. PMID: 30365983 Review.
-
Stearoyl-CoA desaturase as a new drug target for obesity treatment.Obes Rev. 2005 May;6(2):169-74. doi: 10.1111/j.1467-789X.2005.00177.x. Obes Rev. 2005. PMID: 15836467 Review.
Cited by
-
Down-Regulating the High Level of 17-Beta-Hydroxysteroid Dehydrogenase 13 Plays a Therapeutic Role for Non-Alcoholic Fatty Liver Disease.Int J Mol Sci. 2022 May 16;23(10):5544. doi: 10.3390/ijms23105544. Int J Mol Sci. 2022. PMID: 35628360 Free PMC article.
-
Association of HSD17B13 rs72613567: TA allelic variant with liver disease: review and meta-analysis.BMC Gastroenterol. 2021 Dec 20;21(1):490. doi: 10.1186/s12876-021-02067-y. BMC Gastroenterol. 2021. PMID: 34930143 Free PMC article. Review.
-
Rab2A-mediated Golgi-lipid droplet interactions support very-low-density lipoprotein secretion in hepatocytes.EMBO J. 2024 Dec;43(24):6383-6409. doi: 10.1038/s44318-024-00288-x. Epub 2024 Nov 4. EMBO J. 2024. PMID: 39496977 Free PMC article.
-
Combined effects of PNPLA3, TM6SF2 and HSD17B13 variants on severity of biopsy-proven non-alcoholic fatty liver disease.Hepatol Int. 2021 Aug;15(4):922-933. doi: 10.1007/s12072-021-10200-y. Epub 2021 Jun 2. Hepatol Int. 2021. PMID: 34076851 Free PMC article.
-
Associations of Hydroxysteroid 17-beta Dehydrogenase 13 Variants with Liver Histology in Chinese Patients with Metabolic-associated Fatty Liver Disease.J Clin Transl Hepatol. 2021 Apr 28;9(2):194-202. doi: 10.14218/JCTH.2020.00151. Epub 2021 Feb 22. J Clin Transl Hepatol. 2021. PMID: 34007801 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous