Hsd17b6, encoding 17-beta-hydroxysteroid dehydrogenase type 6, catalyzes the synthesis of androsterone and estrone-steroid hormones [2]. It is also involved in maintaining the equilibrium of 5α-dihydrotestosterone (DHT) in the prostate [1]. The SREBP/SCAP/INSIG complex-related pathway seems to be associated with Hsd17b6, and it may play a role in lipid metabolism and steroid homeostasis, which are crucial for normal physiological function [1]. Genetic models, such as gene knockout mouse models, can be used to study its functions.

In a mouse model with Hsd17b6 deletion in the liver (HLKO), hepatic deletion of Hsd17b6 does not affect diet-induced fatty liver disease in terms of fat accumulation, inflammation, and hepatic fibrosis, though its expression is enriched in the liver and correlated with fatty liver disease [2]. In C57BL/6 and NONcNZO10/LtJ T2D mice, hepatic expression of Hsd17b6 and a mutant defective in androgen metabolism improved glucose intolerance, reduced hepatic triglyceride content, and delayed type 2 diabetes (T2D) development by inhibiting SREBP maturation via binding to the SREBP/SCAP/INSIG complex, independent of its sterol oxidase activity [1].

In conclusion, Hsd17b6 is involved in steroid hormone synthesis and lipid-related metabolic regulation. Mouse models, like the HLKO model, have shown that Hsd17b6 is dispensable for diet-induced fatty liver disease, while in T2D mouse models, it plays a role in delaying T2D development. These findings contribute to understanding its functions in metabolic-related diseases and suggest its potential as a therapeutic target for T2D [1,2].

References:

1. Wei, Fengxiang, Gu, Yan, He, Lizhi, Neira, Sandra Vega, Tang, Damu. 2023. HSD17B6 delays type 2 diabetes development via inhibiting SREBP activation. In Metabolism: clinical and experimental, 145, 155631. doi:10.1016/j.metabol.2023.155631. https://pubmed.ncbi.nlm.nih.gov/37330135/

2. Yuan, Delong, Bai, Nan, Zhu, Qihan, Wang, Jianqing, Chen, Yali. 2025. Hepatic HSD17B6 is dispensable for diet-induced fatty liver disease in mice. In Biochemistry and biophysics reports, 41, 101924. doi:10.1016/j.bbrep.2025.101924. https://pubmed.ncbi.nlm.nih.gov/39896111/