Insulin Action And Body Composition In Aged C57bl/6 Mice: A New Model For Obesity

Abstract

The prevalence of obesity in the United States has increased dramatically over the last three decades resulting in a major public health crisis. Feeding mice a high fat diet is a pervasively used model to study mechanisms of human obesity. However, the rapid weight gain that occurs in high fat fed mice and the extremely high fat content of commercially available experimental rodent diets pose serious limitations of this approach. A more appropriate model to study human obesity might be the aged male C57BL/6 mice. PURPOSE: To determine body composition and insulin action in young (YG, 6 months), aged (AG, 18 months), and very old (VO, 28 months) male C57BL/6 mice. METHODS: Body composition was assessed by an LF50 Body Composition Analyzer (Bruker, Inc). Insulin action was determined by conducting insulin tolerance (IT), glucose tolerance (GT), and 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) tolerance (AT) tests. Data was analyzed by using a 1 x 3 analysis of variance and least significant difference post-hoc test. Statistical significance was set at P ≤ 0.05. RESULTS: Body mass (YG: 30.7±1.1 vs AG: 46.3±1.7 vs VO: 39.1±1.6 g) and fat mass (YG: 5.8±1.0 vs AG: 21.6±1.6 vs VO: 10.2±1.8 g) were significantly higher in AG mice compared to VO and YG mice. Lean mass was significantly higher in VO mice compared to AG and YG mice (YG: 20.4±0.4 vs AG: 19.6±0.6 vs VO: 23.4±0.5 g). The area under the curve (AUC) for the GT test was significantly lower in VO mice compared to YG and AG mice (YG: 59030±2817 vs AG: 54835±3423 vs VO: 33378±2286). The AUC for the IT test curve was similar in YG, AG and VO mice (YG: 11320±214 vs AG: 11804±343 vs VO: 11138±968). Although the AUC for the AT test was similar, the decline in glucose following AICAR injections was significantly less in VO mice compared to AG and YG mice, indicating an impairment in AMPK activity. These data suggest that adiposity increases substantially in 18 month old male C57BL/6 mice, a process that appears to be reversed by 28 months. Further, aging does not appear to cause a deterioration in insulin sensitivity when assessed by an IT test. The lower glucose values observed during the GT test in VO mice is likely due to enhanced insulin secretion. Overall our findings indicate that male C57BL/6 mice may be a valuable model to examine mechanisms of obesity when studied at approximately 18 months of age.