Ellagic Acid Supplementation Attenuates Sucrose‐Induced Obesity and Metabolic Complication in C57BL/6 mice

Abstract

High‐sucrose diet causes hepatic steatosis and exacerbates obesity and metabolic complications. Previously, we have demonstrated that ellagic acid (EA), a polyphenol abundantly found in berries, grapes and nuts, inhibits hepatic lipid accumulation in human hepatoma huh7 cells and hyperplastic‐ and hypertrophic‐adipose expansion in human adipocytes. In this study, we hypothesized that EA supplementation inhibits sucrose‐mediated hepatic steatosis and its metabolic consequences. To test this hypothesis, obesity‐prone C57BL/6 male mice were randomly assigned into three isocaloric high‐fat (HF) diets (41% calories from fat) of 1) no‐sucrose (HF), 2) high‐sucrose (37% calories from sucrose, HFHS), or 3) high‐sucrose plus raspberry seed flour equivalent to 0.15% of EA (HFHS‐R). HFHS diet for 8 weeks resulted in a significantly increase in body weight, liver, and adipose tissue mass compared to HF alone, which was normalized by HFHS‐R without altering food intake. Consistently, increases in plasma cholesterol and TG levels in HFHS‐fed mice were markedly dampened by EA supplementation in HFHS‐R. HFHS‐induced hepatic TG accumulation, lipogenic gene expression, and VLDL secretion were also significantly decreased in HFHS‐R comparable to HF alone. Furthermore, systemic levels of glucose and insulin tolerance, and hepatic insulin sensitivity were improved in HFHS‐R group compared to HFHS. Our results implicate that EA supplementation compromises sucrose‐triggered metabolic insults by inhibiting hepatic lipid accumulation. Taken together, our work provides an insight into EA‐containing fruits and vegetables could be developed as promising dietary strategies to prevent sucrose‐triggered obesity and metabolic disorder.