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

Abstract

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 β-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 α (PPARα) and MLX-interacting protein-like (MLXIPL). Therefore, biological sex determines amount of common bean in the diet required to prevent hepatic lipid accumulation.

Consumption of Common Bean Suppresses the Obesogenic Increase in Adipose Depot Mass: Impact of Dose and Biological Sex

“…Scrutiny of the visceral depot data indicates that the mesenteric fat was the most responsive to bean consumption and that the retroperitoneal fat was less responsive in females yet refractory to change in males. While the meaning of these findings and their metabolic relevance is unclear, the impact on the mesenteric depot provides for further interrogation of how bean-mediated effects on the gut microbial community [26,27] and, possibly, the immune system may be linked to effects recently reported on the lipid metabolism in the liver [16].…”

“…The animal feeding study from which the anthropometric data and the tissue analyses described herein were obtained has been reported [16]. Accordingly, the experimental design is briefly summarized, while the laboratory analyses specific to this study are presented in detail.…”

“…Diet formulations were designed to provide equal total caloric energy, as reported in [16]. For convenience, their formulation was included in Supplemental Table S1.…”

“…During this process, samples were pooled (2 samples per pool) according to a similar pattern of weight gain, resulting in total n = 10 pools/group. RNA samples were extracted, sequenced, and analyzed, as reported in [16]. The gene expression data contained 25,683 annotated genes, out of which 21,859 were protein-coding.…”

Vitamin C and vitamin D3 alleviate metabolic-associated fatty liver disease by regulating the gut microbiota and bile acid metabolism via the gut-liver axis

“…Metabolic-associated fatty liver disease (MAFLD), formerly named non-alcoholic fatty liver disease (NAFLD), the prevalence of which has increased alarmingly, places a significant burden on the health and economy of all societies ( Eslam et al, 2020a ; Sarin et al, 2020 ). The use of the new term MAFLD is strongly supported by many countries and regions ( Zhang et al, 2022 ; Chung et al, 2023 ; Lutsiv et al, 2023 ). According to a review and meta-analysis conducted recently, the prevalence of MAFLD in Asia is 29.62% ( Li et al, 2019 ).…”