Selenium binding protein 1 (SBP1) suppresses fructose-induced metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a fatty liver disease that is not caused by alcohol or viral infections, and its prevalence is increasing worldwide. However, the full range of proteins involved in hepatic fat accumulation and their detailed mechanisms remain unclear, and current treatments are limited to symptomatic management. Therefore, the development of novel therapeutic strategies is important. Recently, we reported that selenium binding protein 1 (SBP1) is involved in lipid metabolism. However, its contribution to MASLD has not been elucidated. In the present study, we investigated the effects of SBP1 deficiency on fructose-induced MASLD in SBP1-deficient mice. SBP1 deficiency exacerbates fructose-induced weight gain and hepatic triglyceride accumulation in both males and females. However, changes in hepatic gene expression profiles induced by SBP1 deficiency and fructose intake were sex specific. Among these, stearoyl-CoA desaturase 1 (Scd1) expression was significantly induced by fructose only under SBP1-deficient conditions in both sexes. Given that SCD1 induction contributes to the progression of fatty liver disease, it has been suggested that SBP1 deficiency exacerbates fatty liver disease by inducing SCD1. The findings of this study suggest that modulating SBP1 expression may serve as a potential therapeutic strategy for treating fructose-induced fatty liver disease.