Ellagic acid improves hepatic steatosis and serum lipid composition through reduction of serum resistin levels and transcriptional activation of hepatic ppara in obese, diabetic KK-Ay mice

Ellagic acid (EA) is a polyphenol found in a wide variety of plant foods that not only exhibits free radical-scavenging activity, but also confers protective effects against liver injury. Previously, we reported that pomegranate fruit extract (PFE) had an inhibitory effect on resistin secretion from differentiated murine 3T3-L1 adipocytes and identified EA contained in PFE as a potent suppressor of resistin secretion. Resistin, an adipocytokine, is considered the link between obesity and type 2 diabetes. In this study, we explored whether EA supplementation reduces serum resistin and improves hepatic steatosis and serum lipid profile by using KK-Ay mice fed high-fat diet as a model for obese type 2 diabetes. We found that EA supplementation improved serum lipid profile and hepatic steatosis, and reduced serum resistin levels without altering mRNA expression levels in adipose tissue. Moreover, EA supplementation upregulated mRNA expression of apoa1, ldlr, cpt1a, and ppara genes in the liver. In conclusion, our findings indicate that EA is a potent suppressor of resistin secretion in vivo and a transcriptional activator of ppara in the liver, suggesting a possibility for improving obesity-induced dyslipidemia and hepatic steatosis in KK-Ay mice.