(267) The Influence of Long-Term Western Diet and Voluntary Exercise in an Early Life Stress Mouse Model of Co-Morbid Disorders

Early life stress is associated with the development of chronic pain, mood, and obesity-related metabolic disorders in adulthood. Although the underlying mechanisms of these syndromes are unknown, altered regulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated. It is hypothesized that early life stress induces HPA axis dysfunction leading to the development of overlapping disorders. We have established a mouse model of early life stress, neonatal maternal separation (NMS), that displays molecular evidence of altered HPA axis regulation and urogenital hypersensitivity and dysfunction, which can be mitigated by voluntary exercise. Adult NMS mice also weigh more and have greater body fat percentage than naive mice. Therefore, the present study is investigating whether outcomes of NMS are exacerbated by a Western diet and what effect voluntary exercise has on these outcomes. NMS was performed by separating whole litters from the dam for 3h/day starting on postnatal day 1 (P1) to P21. At 4 weeks of age, NMS and naive (non-separated) male mice either received access to a running wheel in their home cage (exercised) or remained in sedentary housing. At 16 weeks of age, a subset of mice received a high-fat/high-sucrose diet (20% kcal protein, 35% kcal carbohydrate (15% sucrose), 45% kcal fat) for 11 weeks. Perigenital mechanical sensitivity, weight, and body composition were measured throughout the study, and glucose tolerance was measured before sacrifice. Our results suggest that NMS mice were more susceptible to diet-induced weight gain and glucose intolerance compared to naive mice. Additionally, exercise had a stronger protective effect in naive mice, although both NMS and diet had a significant negative impact on running distance. We also observed a significant impact of NMS and diet on perigenital sensitivity. Future work will investigate a potential underlying mechanism for susceptibility to weight gain associated with stress and diet.