Intake of Whole Raspberries and the Raspberry Phytochemicals, Ellagic Acid and Raspberry Ketone Reduces Adiposity, Improves Glucose Control and Changes Hepatic Gene Expression Profiles in High‐fat Fed Mice
Authors: Shay Neil F , Luo Ting , Miranda Omar , Adamson Allysa 
Published: November 2023

The commonly‐available red raspberry, Rubus strigosis, is a relatively understudied nutrient‐dense fruit with both high phytochemical and fiber content. We tested the hypothesis that intake of whole raspberry food products and/or raspberry phytochemicals would remediate metabolic problems in C57BL/6J male mice fed a high‐fat, high‐sucrose diet modeling the obesigenic Western diet (HF).Groups of mice (n=8) were provided either low‐fat diet (LF, 10% kcal fat), high‐fat diet (HF, 45% kcal fat), HF plus Raspberry Juice Concentrate (HF+RJC), HF plus Raspberry Puree Concentrate (HF+RPC), HF plus Raspberry Freeze‐Dried Powder (HF+RFP), HF plus Ellagic Acid (HF+EA), HF plus Raspberry Ketone (HF+RK), or HF plus a combination of EA and RK (HF+E+R) for 10 weeks. Fruit products were provided at 10% of total energy and phytochemicals at ~ 0.2% (w/w) of diet. Animals were fed experimental diets ad libitum; body weight and food intake was recorded weekly. In week nine, a glucose tolerance test was conducted; after ten weeks, animals were killed, serum collected, and liver tissue saved for RNA isolation and gene expression analysis. Glucose tolerance testing indicated that Area Under the Curve (AUC) was generally improved with raspberry supplements vs. HF diet consumption; intake of RFP and E+R produced AUCs essentially equivalent to LF‐fed mice.Weight gain was ameliorated in several groups compared to HF‐fed mice. Intake of HF+RJC, HF+RPC, and HF+E+R significantly reduced weight gain during the study. Food efficiency generally paralleled weight gain.Finally, a custom gene array was used to evaluate the expression of 87 different genes related to various aspects of metabolism, membrane transport, inflammation, and gene transcription factors. The effects of RJC, RPC, EA, or RK intake were evaluated with this focused array system (Qiagen) and Ingenuity Pathway Analysis software (Qiagen). Intake of raspberry foods and pure phytochemicals exerted positive effects on gene expression in the liver. Analysis of relative mRNA levels revealed that these foods and phytochemicals differentially regulated gene expression in multiple cellular pathways associated with the lipid, carbohydrate, and xenobiotic metabolism, antioxidant effect, and inflammation. The HF+RK diet differentially regulated 30 genes, the HF+EA diet 21 genes, the HF+RJC diet 31 genes, and the HF+RPC diet 33 genes, compared with HF diet (P < 0.01–0.1). Interestingly, the consumption of these raspberry products altered the relative mRNA levels so that the pattern of expression more closely resembled that of the mice fed a LF diet rather than the HF‐fed mice. We conclude that although many biological mechanisms may be responsible, clearly, hepatic gene expression is being altered in a favorable manner with the consumption of raspberries and raspberry phytochemicals. Our results allow for the identification of candidate mechanisms by which raspberry phytochemicals may act in metabolic syndrome.Support or Funding InformationNational Processed Raspberry Council (USA)