Abstract 013: Early Life Stress Increases Susceptibility to Develop Obesity and Metabolic Syndrome in a Sex-specific Manner
Recent epidemiological studies demonstrate that women have a greater prevalence of metabolic syndrome with associated increases in fasting glucose not seen in men. Lifestyle factors including diet and physical activity contribute to the risk of developing metabolic disease; however, it has been reported that exposure to early life stress (ELS) has enduring emotional, immune, and metabolic disturbances resulting in increased risk for obesity and type II diabetes. To investigate the effects of ELS as an independent risk factor for metabolic disease, we expose C57Bl/6 mice to maternal separation (MSep), an established behavioral stress model during postnatal life. At weaning, mice were placed on a low-fat diet (LFD, n=6-10) or high-fat diet (HFD, 60% fat calories, n=10) for 16 weeks. Body weight (BW) gain was not different between MSep and control (C) mice when fed a LFD; however, only female MSep mice display higher fat mass compared to C (6.7 ± 0.5 vs. 5.2±0.5 g, p<0.05). Magnetic resonance spectroscopy revealed elevated levels of visceral fat in female MSep mice compared to C, suggesting that MSep increases central adiposity. HFD increased BW in male MSep mice vs C (54.2± 0.7 vs 51.3 ± 0.5, p<0.05); however, BW was dramatically exaggerated in female MSep mice vs. C (48.2± 1.3 vs 34.4 ±2.3 g, p<0.05). Accordingly, fat mass was increased in female MSep mice vs. C (18.2 ± 1.4 vs. 7.6 ± 0 g, p<0.05). Only female MSep exhibited significant impaired glucose tolerance (AUC: 18445±507 vs 22070± 696 AU, p<0.05), hepatomegaly, hypercholesterolemia (156±20 vs. 82 ± 2 mg/dl, p<0.05), hyperleptinemia and hyperinsulinemia (p<0.05) compared to C. Because impaired metabolic function has been linked to inflammation, we characterized splenocytes in female HFD-fed mice. We found a lower population of T-cells but no difference in B-cells in MSep mice vs. C. Functional studies of T cell differentiation demonstrated a reduced capability of naïve T cells to differentiate into anti-inflammatory T regulatory cells in MSep mice vs. C (54± 4 vs. 66± 1 % FoxP3+/CD25+ cells, p<0.05, n=3). The ability to polarize into the pro-inflammatory Th17 phenotype remained intact. These data suggest that the mechanisms by which MSep primes the metabolic responses are sex-specific. NIH R00 HL111354
Author Disclosures: M. Murphy: None. L. Schmuckie: None. D. Powell: None. F. Marti: None. A. Loria: None.
- © 2015 by American Heart Association, Inc.