7,12-dimethylbenz(a)-anthracene (DMBA) & High Fat High Sugar Diet Decrease Physical Activity in Female Mice

Abstract

BACKGROUND: Regular exercise has been shown to diminish the risk of certain cancers. DMBA, (7, 12-dimethylbenz(a)-anthracene) is a complete carcinogen that is used to induce tumors in mice. It has yet to be established whether DMBA has an effect on voluntary wheel running (WR) in mice, and whether these effects may be exacerbated via consumption of a high fat high sugar (HFHS) diet. PURPOSE: Determine if DMBA treatment altered voluntary WR in female SENCAR mice, and whether a HFHS diet exacerbated treatment effects on voluntary WR. METHODS: Offspring of SENCAR breeder pairs were weaned at 3 weeks (wks) of age onto either an ad lib fed HFHS (20% protein, 45% fat/24% sucrose + 10% fructose water) or a diet restricted (DR) (12% kcal restriction, 20% protein, 10% fat, 57% cornstarch) diet. Animals were double-housed and randomly assigned to either a DMBA (n=40) treatment with HFHS (n=20) and DR (n=20) diets; or a control (CNTL) (n=18) treatment with HFHS (n=10) and DR (n=8) diets. At 4 wks of age, two plastic running wheels were mounted inside standard rat cages, and connected to a computer to record WR duration and distance. At 7-9 wks of age, mice were gavaged with DMBA dissolved in corn oil (20 μg/mouse/day) or with corn oil vehicle only (CNTL) for 5 days/wk for 6 weeks. A two-way ANOVA was employed to determine the effect of DMBA on activity with factors of treatment and diet for wks 9-20. RESULTS: Compared to CNTL, DMBA significantly decreased distance (7.41 ± 0.45 vs. 11.08 ± 0.68 km/day; p=0.0002), and duration (175.19 ± 8.24 vs. 261.23 ± 12.36 min; p<0.0001). No significant difference in speed was noted (40.31 ± 1.37 vs. 40.34 ± 2.05 m/min; p=0.77). HFHS diet compared to DR diet significantly decreased distance (5.84 ± 0.60 vs. 11.08 ± 0.55 km/day; p<0.0001), duration (168.41 ± 10.9 vs. 233.14 ± 10.1 min; p<0.0001), and speed (33.04 ± 1.81 vs. 47.12 ± 1.67 m/min; p<0.0001). No significant interactions were observed between treatment and diet groups. CONCLUSIONS: DMBA and HFHS diet decrease WR distance and duration, while only the HFHS diet decreased WR speed. Although DMBA and HFHS independently decreased WR, a lack of interaction suggest that they are not additive or synergistic. ACKNOWLEDGMENTS: Project was funded by the US Army through the Department of Defense projects W81XWH-13-1-0278 (Fuchs-Young) and W81XWH-13-1-0279 (Lightfoot).