Mouse Strain Differences in Female Mice Fed a Short‐Term Western Diet

Abstract

Mouse models of diet‐induced obesity are commonly used for studies of metabolic disease. Since sex and strain differences are suggested to influence the results, studies have been generally limited to males of one mouse strain. This limited study population may impact the understanding of the effect of sex and genetic background on metabolic parameters. Therefore, the purpose of this study was to examine potential differences in short‐term feeding of a high fat diet in two popular strains of female mice. Ten‐week‐old, female FVB/N (FVB, n=20) and C57BL/6‐Ncrl (C57, n=20) mice were fed a Western Diet (WD; 40% calories from fat) or standard chow diet (13% calories from fat) for 6 weeks. Body weight was measured at weekly intervals and the Open Field Test (OFT) was administered to assess changes in activity and behavior at baseline and 6 weeks. The OFT consists of a circular arena, where mice were observed for 10 minutes using a video tracking software system to determine distance, speed, and motion. Tissues and blood were harvested after the 6‐week feeding period. Body weights and organ masses (i.e., heart, liver, adipose, and spleen) were significantly greater in FVB‐chow compared to C57‐chow mice. After 6‐weeks of feeding, body weights, adipose mass, and liver mass were significantly higher in FVB‐WD but not in C57‐WD compared to respective chow groups. FVB‐WD had reduced heart weight to tibial length ratios (FVB‐WD: 6.05±0.14 vs. FVB‐chow: 5.41±0.14, P<0.05) and higher serum ketone body levels compared to FVB‐chow (FVB‐WD: 0.42±0.03 vs. FVB‐chow: 0.76±0.15 mM, P<0.05), changes that were not observed in C57‐WD. OFT results revealed significant effects of diet and mouse strain. At baseline, FVB mice spent greater time moving (422± vs. 379±11 sec, P<0.05) and greater time in the border zone (515±9 vs. 452±11 sec, P<0.05) compared to C57 mice. After 6 weeks, time spent moving tended to decrease in C57‐WD compared to C57‐Chow (42% vs. 30%, P<0.10) while FVB‐WD and FVB‐chow had similar decreases (15% vs. 13% in FVB‐chow). Time in the border zone significantly increased by 8% in C57‐WD compared to a 20% decrease in C57‐chow. In contrast, border zone time decreased by 9% and 10% in FVB‐chow and FVB‐WD, respectively. In summary, in response to 6 weeks of WD, female FVB mice exhibit a more pronounced physical phenotype whereas female C57 mice are more prone to changes in activity and behavior. Overall, these results highlight important strain differences in response to a short‐term high fat diet in female mice