Graduate Thesis Or Dissertation
 

Metabolic Implications of Red Raspberry Polyphenol Supplementation in High Fat-Fed C57BL/6J Mice

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https://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/r207tw54p

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  • Objective: Red raspberries are rich in polyphenols and fiber, relatively low in sugar compared with other fruits, and have been demonstrated to have favorable effects on energy homeostasis in mice. However, it has been unclear precisely which compounds within red raspberries possess the greatest bioactivity, and their mechanism of action. Two extracts were prepared from red raspberries, enriched in either hydrophilic or hydrophobic polyphenols. We tested the hypothesis that these two polyphenol extracts would differentially alter and improve physiological measures and the hepatic transcriptome of C57BL/6J male mice fed a high fat diet (HF), enriched with cholesterol and sucrose to emulate an obesogenic western diet. Methods: Raspberry polyphenol extracts were obtained using FPX-66 resin and eluted with 25% and 80% ethanol solutions. Polyphenol extracts were partially oven dried, then freeze dried. Groups of mice were provided either a low fat diet (LF, 10%kcal fat, n=12), high fat diet (HF, 45% kcal fat, n=12), high fat died with added raspberry puree concentrate (RPC, n=8), high fat diet with added hydrophilic raspberry polyphenol extract (R25, n=8), or high fat diet with added hydrophobic raspberry polyphenol extract (R80, n=8) ad libitum for 10 weeks. Body weights, food intake, and glucose tolerance were measured. Post mortem, serum was collected for ELISAs, organ weights were recorded, and liver tissue was collected for triglyceride analysis and differential expression analysis (DEA). Messenger RNA was isolated from liver tissue and sequenced by Thermo Fischer Scientific. Results: Energy efficiency, liver weights, and the adipose to body weight ratio in the R25 and R80 groups was intermediate to the LF and HF controls. Fasting blood glucose, serum triglycerides, and adipose tissue weights did not significantly differ between treatment groups. A trend toward significance was seen in a reduction of weight gain in the raspberry treatment groups. Differential expression analysis of the mouse groups revealed that the R25 diet acted agonistically towards the constitutive androstane receptor (CAR) and depressed the activities of several sterol regulatory binding proteins (SREBPs). The R80 diet acted agonistically toward the peroxisome proliferator-activated receptor alpha (PPARα). Conclusions: Supplementation of a high fat diet with raspberry polyphenols extracts was able to improve liver function and energy efficiency in C57 mice. The hydrophilic raspberry polyphenol extract behaved as an agonist for the PPARα receptor, while the hydrophobic raspberry polyphenol extract behaved as an agonist for the CAR receptor. These findings suggest that select polyphenols found within red raspberries may serve as nutraceuticals that specifically target PPARα and CAR in liver.
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  • 112 pages
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  • Pending Publication
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  • 2020-06-10 to 2022-07-11

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