Bitter melon fruit extract affects hepatic expression of the genes involved in inflammation and fatty acid metabolism in ob/ob mice

Abstract

Background: The fruit of bitter melon (Momordica charantia L.) has traditionally been used as a crude drug to treat obesity and diabetes mellitus. Previously, we reported that an ethyl acetate (EtOAc)-soluble fraction of bitter melon fruit extract showed anti-inflammatory effects on interleukin-1β-treated rat hepatocytes. The liver plays a pivotal role to maintain homeostasis of glucose and lipid. It is speculated that the administration of an EtOAc-soluble fraction of a bitter melon fruit extract (BMFA) may change the expression profile of hepatic genes involved in inflammation, glucose metabolism, and lipid metabolism.

Objective: We aimed to evaluate the effects of BMFA on the gene expression in the liver of ob/ob mice, which are deficient in leptin and are used as a diabetes mellitus model. The changes may be related to hepatic steatosis and obesity.

Methods: Male 8-week-old ob/ob mice (average body weight, 40.9 g) were fed a standard diet with and without BMFA (ob/ob+BMFA and ob/ob–BMFA groups, respectively; 4 mice/group) for seven days. The livers were excised to prepare total RNA for microarray expression analyses. Signal ratios (i.e., ob/ob+BMFA versus ob/ob–BMFA group) were calculated to compare gene expression.

Results: The mRNA levels of 2,632 genes were significantly changed in the livers of ob/ob+BMFA mice when compared with those of ob/ob–BMFA mice. As expected, proinflammatory cytokine and chemokine genes were significantly downregulated by BMFA. The acyl-Coenzyme A thioesterase 3 gene in fatty acid oxidation was upregulated in ob/ob+BMFA liver, whereas free fatty acid receptor 2 and solute carrier family 27 member 3 genes were downregulated. Most genes involved in glycolysis and gluconeogenesis were not affected by BMFA. In contrast, the level of peroxisome proliferator-activated receptor γ coactivator 1α mRNA significantly increased in ob/ob+BMFA mice, suggesting that BMFA administration may reduce insulin resistance in ob/ob mice.

Conclusion: Our study suggested that BMFA may possess anti-inflammatory effects and enhance fatty acid metabolism in ob/ob mouse liver. These data imply the possibility that EtOAc-soluble constituents in bitter melon fruit may improve lipid accumulation in the liver during obesity and diabetes mellitus, as well as non-alcoholic fatty liver disease.

Keywords: Momordica charantia, gene expression, inflammation, diabetes mellitus, non-alcoholic fatty liver disease.