AIM: To characterize the influence of diet-induced changes in body fat on colitis severity in SlVlAD3-/- mice.METHODS: SMAD3-/- mice (6-8 wk of age) were ran- domly assigned to receive a calorie restricted (30% o...AIM: To characterize the influence of diet-induced changes in body fat on colitis severity in SlVlAD3-/- mice.METHODS: SMAD3-/- mice (6-8 wk of age) were ran- domly assigned to receive a calorie restricted (30% of control; CR), control (CON), or high fat (HF) diet for 20 wk and were gavaged with sterile broth or with Helicobacter hepaticus (H. hepaticus) to induce colitis. Four weeks after infection, mice were sacrificed and the cecum and colons were processed for histological evaluation.RESULTS: Dietary treatment significantly influenced body composition prior to infection (P 〈 0.05), with CR mice having less (14%±2%) and HF-fed mice more body fat (32% ± 7%) compared to controls (22%±4%). Differences in body composition were associated with alterations in plasma levels of leptin (HF 〉 CON 〉 CR) and adiponectin (CON 〉 HF 〉/ CR) (P 〈 0.05). There were no significant differences in colitis scores between CON and HF-fed mice 4 wk post-infection. Consistent with this, differences in proliferation and in- flammation markers (COX-2, iNOS), and infiltrating cell types (CD3^+ T lymphocytes, macrophages) were not observed. Unexpectedly, only 40% of CR mice survived infection with H. hepaticus, with mortality observed as early as I wk following induction of colitis.CONCLUSION: Increased adiposity does not influence colitis severity in SMAD3-/- mice. Importantly, caloric restriction negatively impacts survival following pathogen challenge, potentially due to an impaired immune response.展开更多
文摘AIM: To characterize the influence of diet-induced changes in body fat on colitis severity in SlVlAD3-/- mice.METHODS: SMAD3-/- mice (6-8 wk of age) were ran- domly assigned to receive a calorie restricted (30% of control; CR), control (CON), or high fat (HF) diet for 20 wk and were gavaged with sterile broth or with Helicobacter hepaticus (H. hepaticus) to induce colitis. Four weeks after infection, mice were sacrificed and the cecum and colons were processed for histological evaluation.RESULTS: Dietary treatment significantly influenced body composition prior to infection (P 〈 0.05), with CR mice having less (14%±2%) and HF-fed mice more body fat (32% ± 7%) compared to controls (22%±4%). Differences in body composition were associated with alterations in plasma levels of leptin (HF 〉 CON 〉 CR) and adiponectin (CON 〉 HF 〉/ CR) (P 〈 0.05). There were no significant differences in colitis scores between CON and HF-fed mice 4 wk post-infection. Consistent with this, differences in proliferation and in- flammation markers (COX-2, iNOS), and infiltrating cell types (CD3^+ T lymphocytes, macrophages) were not observed. Unexpectedly, only 40% of CR mice survived infection with H. hepaticus, with mortality observed as early as I wk following induction of colitis.CONCLUSION: Increased adiposity does not influence colitis severity in SMAD3-/- mice. Importantly, caloric restriction negatively impacts survival following pathogen challenge, potentially due to an impaired immune response.