Metabolic effects of consumption of quercetin, ellagic acid, cherry, and apple phytochemical extracts in high-fat fed mice Public Deposited

http://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/w3763899g

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  • Metabolic improvements and changes in gene expression were measured in mice fed polyphenol-rich extracts derived from apples and sweet cherries, and the common phytochemicals, quercetin and ellagic acid. Polyphenol-rich extracts were produced by solid phase extraction and column chromatography. Extracts and purified compounds were mixed into a high-fat (HF, 60% of total kcal) obesigenic rodent diet and fed to C57BL/6J mice along with low-fat (LF, 10% of total kcal) and HF+treatment (HF+X) diets. Mice fed the HF control diet became obese and lost normal glucose control. Although no changes in weight gain or diet consumption were seen among the mice fed the high-fat diets, mice fed HF+X diets containing extracts and purified compounds exhibited improved metabolic parameters compared to mice fed the HF control diet. For example, six-hour fasted blood glucose levels measured at week six in mice fed HF+X diets, or HF diet supplemented with apple (HF+AE) or cherry extract (HF+CE), quercetin (HF+QUE), or ellagic acid (HF+EA), showed lower baseline blood glucose levels when compared with the HF-fed mice (p=<0.05). Glucose tolerance was also marginally improved in the HF+AE- and HF+QUE-fed mice (p=<0.10). A grip test, measuring strength, showed a trend toward improved strength in the HF+treatment groups when compared to HF-fed mice. Treadmill-like Rotarod testing evidenced a trend for improved endurance and balance in all HF+X groups, but with no significance. Serum cytokine levels measured at the end of the study demonstrated reduced levels of several inflammatory factors in HF+X-fed mice, indicating improved anti-inflammatory regulation compared to HF-fed mice. Finally, HF+X-fed mice showed increased relative expression for markers of fatty acid oxidation, such as CPT1-α, and ACOX-1, which was consistent with qualitative examination of lipid accumulation in liver tissue sections. Quantitative measurements of cellular lipid accumulation were measured using a human HepG2 cell line model. HepG2 cells were treated with oleic acid (OA) to induce lipid accumulation along with the treatment compound of interest. Cells were then stained with Oil Red O and hepatic fat accumulation was measured using a spectrophotometer. Cells exposed to OA+QUE showed a significant decrease in lipid accumulation (p=<0.05) and other treatment groups showed a similar or slightly increased degree of lipid accumulation. Therefore, we conclude that compounds present in apples and cherries, quercetin and ellagic acid produce beneficial metabolic effects and that part of this improvement is mediated by phytochemical activation of nuclear hormone receptors.
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