Thwarting Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) with Common Bean: Dose- and Sex-Dependent Protection against Hepatic Steatosis

Hepatic steatosis signifies onset of metabolic dysfunction-associated fatty liver disease (MAFLD) caused by disrupted metabolic homeostasis compromising liver function. Regular consumption of common beans reduces the risk of metabolic impairment, but its effective dose, the impact of biological sex, and underlying mechanisms of action are unknown. We fed female and male C57BL6/J mice with obesogenic yet isocaloric diets containing 0%, 17.5%, 35%, and 70% of total dietary protein derived from cooked whole common beans. Liver tissue was collected for histopathology, lipid quantification, and RNA-seq analyses. Beans qualitatively and quantitatively diminished hepatic fat deposition at the 35% dose in female and 70% dose in male mice. Bean-induced differentially expressed genes (DEGs) most significantly mapped to hepatic steatosis and revealed dose-responsive inhibition of de novo lipogenesis markers (Acly, Acaca, Fasn, Elovl6, Scd1, etc.) and triacylglycerol biosynthesis, activation of triacylglycerol degradation, and downregulation of sterol regulatory element-binding transcription factor 1 (SREBF1) signaling. Upregulated fatty acid beta-oxidation was more prominent in females, while suppression of Cd36-mediated fatty acid uptake-in males. Sex-dependent bean effects also involved DEGs patterns downstream of peroxisome proliferator-activated receptor alpha (PPAR alpha) and MLX-interacting protein-like (MLXIPL). Therefore, biological sex determines amount of common bean in the diet required to prevent hepatic lipid accumulation.

Automated summary

Hepatic steatosis indicates the beginning of metabolic dysfunction-associated fatty liver disease (MAFLD) due to disrupted metabolic homeostasis, which affects liver function. Regular consumption of common beans has been found to reduce the risk of metabolic impairment, but the required dose, the impact of biological sex, and the underlying mechanisms are unknown. In this study, female and male mice were fed obesogenic yet isocaloric diets containing different amounts of protein derived from cooked whole common beans. The results showed that beans reduced hepatic fat deposition at specific doses in both female and male mice. The differentially expressed genes (DEGs) induced by beans were mainly involved in hepatic steatosis and demonstrated dose-responsive inhibition of de novo lipogenesis markers, activation of triacylglycerol degradation, and downregulation of SREBF1 signaling. Additionally, the effects of beans on fatty acid metabolism differed between females and males. The findings suggest that the amount of common beans in the diet required to prevent hepatic lipid accumulation depends on biological sex.