Investigating How Diet-Microbiota-Host Interactions Influence the Development of Diet-Induced Obesity in Female Mice

Obesity, defined as the abnormal accumulation of fat with a body mass index (BMI) ≥ 30 kg/m2, has become a worldwide health problem. Numerous human and animal studies have investigated how various factors influence the development of obesity. An interaction between high-fat, high-sugar Western diet (WD) consumption and the gut microbiota promotes obesity in male C57BL/6 (B6) and C3H/HeN (C3H). However, experimental data showing the effect of WD on female germ-free (GF) and conventionalized (CVZ) mice are lacking. We therefore tested whether a WD could induce obesity and metabolic disease phenotypes in female GF and CVZ B6 and C3H mice compared to a low-fat (LF) control diet. We also evaluated the composition of the gut microbiome in female CVZ B6 and C3H mice fed a WD. We observed that female GF C3H, like their CVZ counterparts, gained significantly more body weight when fed a WD but not GF B6 mice. We then hypothesized that WD consumption would promote fat mass accretion, promote metabolic aberrancies, and restructure the gut microbiota to support the development of obesity in female mice in a host genotype-dependent manner. Our results showed that feeding a WD increased white adipose tissue weight and blood glucose levels in GF C3H but not GF B6 mice. Additionally, we found that feeding a WD caused changes in leptin and resistin in female C3H mice. Results from 16S RNA gene sequencing analysis showed that WD feeding altered gut microbiota composition in both CVZ B6 and C3H female mice. Importantly, these results demonstrated a requirement for the gut microbiota in weight gain in female B6 but not C3H mice during WD consumption, which is similar to what has been reported previously for male mice. These findings are important because they provide a more complete understanding for the role of the gut microbiota in diet-induced obesity in female subjects and may ultimately help further the development of novel preventative strategies for obesity based on gender. Advisor: Amanda E. Ramer-Tai