Effect of Polyphenol-Rich Extract from Walnut on Diet-Induced Hypertriglyceridemia in Mice via Enhancement of Fatty Acid Oxidation in the Liver

Abstract

The kernel pellicles of walnut are rich in ellagitannins with antioxidative activity. A polyphenol-rich extract from walnuts (WP, 45% polyphenol) was prepared and evaluated for its hypolipidemic effect in high fat diet fed mice. Oral administration of WP (100 and 200 mg/kg) significantly reduced liver weight and liver and serum triglycerides (TG). Hepatic beta-oxidation in cytosol, including peroxisome, was enhanced by WP (50-200 mg/kg). mRNA expressions of hepatic peroxisome proliferator-activated receptor (PPAR) alpha and acyl coenzyme A oxidase (ACOX) 1 were enhanced by WP (50-200 mg/kg). With respect to the hypotriglyceridemic mechanism of WP, it suppressed neither olive oil induced serum TG elevation in mice nor oleic acid induced TG accumulation in HepG2 cells. On the other hand, mRNA expressions of PPARalpha, ACOX1, and carnitine palmitoyltransferase (CPT) 1A in HepG2 cells were significantly enhanced by addition of WP (100 microg/mL). Moreover, tellimagrandin I, a polyphenolic constituent in WP, enhanced ACOX1 expression at 1-100 microg/mL. In conclusion, WP was found to possess hypotriglyceridemic activity via enhancement of peroxisomal fatty acid beta-oxidation in the liver. These results suggest that tellimagrandin I is involved in the hypotriglyceridemic mechanism of WP.