Studying the pharmacogenomic effect of cranberry extract on reducing body weight using collaborative cross mice

Abstract

The non-dialyzable material (NDM) of polyphenol-rich cranberry extract (CRE) powder (NDM-CRE) was studied for its effect of inducing body weight (BW) loss in 13 different mouse lines with well-defined genetically diverse backgrounds, named the collaborative cross (CC). From the age of 8 weeks, the mice were maintained on a high-fat diet (HFD) for 18 weeks, to induce obesity, and BW was measured biweekly. From week 12, CRE was injected intraperitoneally (IP) (50 mg kg⁻¹) 3 times a week per mouse for a 6 week period. Statistical analysis results have shown a significant increase in body weight between week 0 and week 12; the increase in BW of 13 lines of mice on HFD was in the range of 10.41% to 68.65% for males and 9.78% to 64.74% for females. After injecting NDM-CRE extract, our analysis has shown an induced change in BW between week 12 and week 18. In males, NDM-CRE caused a significant decrease in BW of 5 out of the 13 lines in the range of −5.68% to −16.69% and a significant increase of 8.31% in BW of one male line, whereas in seven lines there was no significant decrease (−2.14% to −4.09%). In females, NDM-CRE caused a significant decrease in BW of 5 out of the 13 lines in the range of −3.90% to −11.83%, whereas in eight lines there were no significant changes in BW and it ranged between −1.50% and 4.90%. The broad-sense heritability (H²) and genetic coefficient of variation (CV_g) were estimated and found to be between 0.71 and 0.81 for H², and 0.18 and 0.24 for CV_g of females and males, respectively, with respect to the efficacy of NDM-CRE on body weight reduction. Our results have shown that hosts with different genetic backgrounds respond differently to body weight increase, as well as to NDM-CRE treatment for body weight reduction. These results provide a platform for assessing more CC lines and mapping genes underlying the efficacy of the NDM-CRE treatment as a way of understanding pharmacogenomics.