Hsd17b13-KO Mouse

HSD17B13, hydroxysteroid 17-β dehydrogenase family 13, is a liver-specific, lipid droplet-associated protein [3,5,8]. It has enzymatic pathways involving steroids, pro-inflammatory lipid mediators and retinol [8]. The 17β-Hydroxysteroid dehydrogenases (HSD17Bs) family, to which HSD17B13 belongs, is mainly involved in sex hormone metabolism, and some members also play roles in cholesterol and fatty acid metabolism [3]. Genetic models, such as gene knockout in mice, are valuable for studying its functions.

In mice, knockdown of Hsd17b13 protects against liver fibrosis in non-alcoholic steatohepatitis, associated with decreased pyrimidine catabolism at the level of dihydropyrimidine dehydrogenase [2]. Also, hepatic overexpression of HSD17B13 in mice promotes lipid accumulation in the liver [3]. The rs72613567-TA variant in HSD17B13, which leads to a loss-of-function, is associated with reduced risk of chronic liver diseases in humans and mitigates liver injury in mouse models [4]. Adeno-associated viral-mediated xeno-expression of human HSD17B13 exacerbates western diet/carbon tetrachloride-induced liver inflammation in Hsd17b13-/-mice [7].

In conclusion, HSD17B13 plays a role in hepatic lipid homeostasis and liver inflammation. Loss-of-function models, including gene knockout in mice, have revealed its contribution to the development of non-alcoholic fatty liver disease (NAFLD), liver fibrosis, and chronic liver inflammation. These findings suggest HSD17B13 could be a potential therapeutic target for treating related liver diseases [1,2,3,4,5,6,7,8,9].

References:

1. Zhang, Hai-Bo, Su, Wen, Xu, Hu, Zhang, Xiao-Yan, Guan, You-Fei. 2022. HSD17B13: A Potential Therapeutic Target for NAFLD. In Frontiers in molecular biosciences, 8, 824776. doi:10.3389/fmolb.2021.824776. https://pubmed.ncbi.nlm.nih.gov/35071330/

2. Luukkonen, Panu K, Sakuma, Ikki, Gaspar, Rafael C, Petersen, Kitt Falk, Shulman, Gerald I. 2023. Inhibition of HSD17B13 protects against liver fibrosis by inhibition of pyrimidine catabolism in nonalcoholic steatohepatitis. In Proceedings of the National Academy of Sciences of the United States of America, 120, e2217543120. doi:10.1073/pnas.2217543120. https://pubmed.ncbi.nlm.nih.gov/36669104/

3. Su, Wen, Mao, Zhuo, Liu, Yiao, Gustafsson, Jan-Ake, Guan, Youfei. 2018. Role of HSD17B13 in the liver physiology and pathophysiology. In Molecular and cellular endocrinology, 489, 119-125. doi:10.1016/j.mce.2018.10.014. https://pubmed.ncbi.nlm.nih.gov/30365983/

4. Abul-Husn, Noura S, Cheng, Xiping, Li, Alexander H, Gromada, Jesper, Dewey, Frederick E. . A Protein-Truncating HSD17B13 Variant and Protection from Chronic Liver Disease. In The New England journal of medicine, 378, 1096-1106. doi:10.1056/NEJMoa1712191. https://pubmed.ncbi.nlm.nih.gov/29562163/

5. Motomura, Takashi, Amirneni, Sriram, Diaz-Aragon, Ricardo, Florentino, Rodrigo M, Soto-Gutierrez, Alejandro. 2021. Is HSD17B13 Genetic Variant a Protector for Liver Dysfunction? Future Perspective as a Potential Therapeutic Target. In Journal of personalized medicine, 11, . doi:10.3390/jpm11070619. https://pubmed.ncbi.nlm.nih.gov/34208839/

6. Wang, P, Wu, C-X, Li, Y, Shen, N. . HSD17B13 rs72613567 protects against liver diseases and histological progression of nonalcoholic fatty liver disease: a systematic review and meta-analysis. In European review for medical and pharmacological sciences, 24, 8997-9007. doi:10.26355/eurrev_202009_22842. https://pubmed.ncbi.nlm.nih.gov/32964989/

7. Ye, Jing, Huang, Xiyu, Yuan, Manman, Xu, Qiang, Wu, Xingxin. . HSD17B13 liquid-liquid phase separation promotes leukocyte adhesion in chronic liver inflammation. In Journal of molecular cell biology, 16, . doi:10.1093/jmcb/mjae018. https://pubmed.ncbi.nlm.nih.gov/38692847/

8. Amangurbanova, Maral, Huang, Daniel Q, Loomba, Rohit. 2022. Review article: the role of HSD17B13 on global epidemiology, natural history, pathogenesis and treatment of NAFLD. In Alimentary pharmacology & therapeutics, 57, 37-51. doi:10.1111/apt.17292. https://pubmed.ncbi.nlm.nih.gov/36349732/

9. Stender, Stefan, Romeo, Stefano. . HSD17B13 as a promising therapeutic target against chronic liver disease. In Liver international : official journal of the International Association for the Study of the Liver, 40, 756-757. doi:10.1111/liv.14411. https://pubmed.ncbi.nlm.nih.gov/32255570/