| Summary: | This study aimed to investigate the beneficial effects of <i>Momordica charantia</i> (MC) extract and MC fermented with <i>Leuconostoc mesenteroides</i> MKSR (FMC) on high-fat and high-cholesterol diet-induced metabolic complications. Male C57BL/6 mice were divided into six groups: normal diet (ND), high-fat and high-cholesterol diet (HFCD), HFCD with 1% MC extract (HFCD + 1M), HFCD with 4% MC extract (HFCD + 4M), HFCD with 1% fermented MC (HFCD + 1F), and HFCD with 4% fermented MC (HFCD + 4F). After 12 weeks of dietary intervention, the consumption of MC fermented with <i>L. mesenteroides</i> MKSR resulted in significant decreases in white adipose tissue weights (epididymal adipose tissue and retroperitoneal adipose tissue), serum alanine aminotransferase activity, and hepatic triglyceride levels. FMC also lowered total hepatic cholesterol content, improved glucose clearance during the oral glucose tolerance and insulin tolerance tests, and increased fecal cholesterol efflux from the enterohepatic circulation. Furthermore, the FMC notably increased hepatic mRNA expressions, which may indicate a compensatory mechanism against induced cholesterol efflux. Moreover, FMC induced both adipogenic (sterol regulatory element-binding protein 1c) and lipolytic (lipoprotein lipase, peroxisome proliferator-activated receptor alpha, and <i>adiponectin</i>) mRNA expressions. These findings suggest that fermentation with the probiotic <i>L. mesenteroides</i> MKSR enhances the beneficial effects of MC, preventing metabolic complications associated with a high-fat diet.
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