1992-P: Early and Chronic Exposure to Penicillin Increases Obesity and Insulin Resistance in High-Fat Diet-Fed Mice

Abstract

Increasing prevalence of antibiotic use may have health consequences given their effects on gut microbiome. Male and female C57BL/6J mice were exposed to a low-dose penicillin (7 mg/L) during the first 4 weeks of life via maternal drinking water (PCN; n=6-10) or continuously (PCN-C; n=4-5), and a high-fat diet (HFD) was started at 6 weeks of age. Whole body fat mass began to increase in male PCN and PCN-C groups after 5 weeks of HFD (Figure 1). This was largely due to 20% decrease in physical activity in PCN mice. Insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp after 20 weeks of HFD, and glucose infusion rate (GIR) and glucose turnover (GT) were significantly reduced in PCN-C group. The PCN group showed increased hepatic insulin resistance compared to Control (n=12; Figure 2). In female mice, PCN effects were more pronounced with increased fat mass after 1 week of HFD (Figure 3). This was due to 30% decrease in physical activity in female PCN mice compared to Control (n=5). After 20 weeks of HFD, female Control mice remained insulin sensitive, but female PCN-C mice developed insulin resistance with 20% decreases in GIR and GT (Figure 4). In conclusion, these results show that early life or chronic exposure to penicillin negatively affects energy balance and glucose metabolism in mice with larger effects in female mice. Our findings indicate an important role of antibiotic exposure in obesity and insulin resistance. Disclosure H. Noh: None. S. Suk: None. R.H. Friedline: None. X. Hu: None. D.A. Tran: None. L.A. Tauer: None. J. Choi: None. M. Ko: None. B. Kim: None. T. Surapaneni: None. M.J. Blaser: None. J.K. Kim: None. Funding National Institutes of Health (5U2C-DK093000)