Common Bean Suppresses Hepatic Ceramide Metabolism in a Mouse Model of Metabolic Dysfunction-Associated Steatotic Liver Disease

菜豆抑制代谢功能障碍相关脂肪肝小鼠模型中的肝神经酰胺代谢

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作者:Vanessa K Fitzgerald, Tymofiy Lutsiv, John N McGinley, Elizabeth S Neil, Mary C Playdon, Henry J Thompson

Conclusions

Bean incorporation into an otherwise obesogenic diet induces effects on synthesis, biotransformation, and degradation of sphingolipids that inhibit the accumulation of ceramide species that exert pathological activity. These effects are consistent with a mechanistic role for altered sphingolipid metabolism in explaining how bean inhibits the development of MASLD.

Methods

A cohort of C57BL/6 mice were randomized into experimental diets containing multiple dietary concentrations of common bean. The primary endpoint of this study was comparing metabolomic analyses from liver and plasma of different treatment groups. Additionally, RNA sequencing and protein expression analysis via nanocapillary immunoelectrophoresis were used to elucidate signaling mediators involved.

Results

Herein, global metabolomic profiling of liver and plasma identified sphingolipids as a lipid subcategory on which bean consumption exerted significant effects. Of note, C16 and C18 ceramides were significantly decreased in bean-fed animals. Hepatic RNAseq data revealed patterns of transcript expression of genes involved in sphingolipid metabolism that were consistent with metabolite profiles. Conclusions: Bean incorporation into an otherwise obesogenic diet induces effects on synthesis, biotransformation, and degradation of sphingolipids that inhibit the accumulation of ceramide species that exert pathological activity. These effects are consistent with a mechanistic role for altered sphingolipid metabolism in explaining how bean inhibits the development of MASLD.

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