Abstract P152: Female Mice Are Not Protected From High Fat Diet-induced Metabolic Dysfunction

Abstract

Female clinical populations are generally protected from obesity-related blood pressure and metabolic complications such as hypertension and type II diabetes, despite increased adiposity compared to males. Similar cardiovascular protection has been observed in obese female mice produced by high fat diet (HFD) feeding, a well-established animal model of obesity. The impact of HFD on glucose homeostasis and insulin action in relation to gender differences, however, remains unclear. In this study, we tested the hypothesis that female mice would be protected from HFD-induced glucose intolerance and insulin resistance. To test this, five-week old male and female C57BL/6J mice were placed on control chow diet or 60% HFD for 12 weeks (n=11 chow male; n=6 chow female; n=15 HFD male; n=5 HFD female). Body composition was measured and glucose tolerance testing (GTT; 2g/kg of 50% dextrose) and insulin tolerance testing (ITT; 0.75 units/kg) were performed during the last week of diet. Females had lower body mass compared with males over the 12-week study period. Both genders increased body mass to a similar extent in response to chow diet (24.6±1.7 male vs. 26.5±2.3% female; p=0.517), and HFD (85.0±2.1 males vs. 79.8±6.7% females; p=0.332). HFD females had similar adiposity compared with males (22.9±0.7 males vs. 22.5±1.6% females; p=0.780). HFD reduced insulin sensitivity in male mice [area under the curve (AUC) for blood glucose levels during ITT: -5903±662 chow vs. -1748±1024 HFD; p=0.005] and female mice (-6599±966 chow vs. -2904±1507 HFD; p=0.041), with no differences between genders (p=0.567). HFD also resulted in glucose intolerance in male (AUC for blood glucose levels during GTT: 40262±1769 chow vs. 52800±2502 HFD; p=0.001) and female (36951±2270 chow vs. 55507±3582 HFD; p=0.001) mice, with no gender differences (p=0.582). These data suggest that in contrast to our hypothesis, HFD female mice develop obesity-related insulin resistance and glucose intolerance to a similar extent as males. These findings have important implications for use of this mouse model to study impact of gender on metabolic function in obesity.