INSERM Unit 1073 «Nutrition, Inflammation and Dysfunction of the Gut-Brain Axis», Rouen University, Rouen, France; Institute for Research and Innovation in Biomedicine, Rouen University, Rouen, France; Nutrition Unit, Rouen University Hospital, Rouen, France.
INSERM Unit 1073 «Nutrition, Inflammation and Dysfunction of the Gut-Brain Axis», Rouen University, Rouen, France; Institute for Research and Innovation in Biomedicine, Rouen University, Rouen, France.
Clin Nutr. 2014 Dec;33(6):1046-53. doi: 10.1016/j.clnu.2013.11.006. Epub 2013 Nov 15.
BACKGROUND & AIMS: Anorexia nervosa is a severe eating disorder often leading to malnutrition and cachexia, but its pathophysiology is still poorly defined. Chronic food restriction during anorexia nervosa may induce gut barrier dysfunction, which may contribute to disease development and its complications. Here we have characterized intestinal barrier function in mice with activity-based anorexia (ABA), an animal model of anorexia nervosa.
Male C57Bl/6 ABA or limited food access (LFA) mice were placed respectively in cages with or without activity wheel. After 5 days of acclimatization, both ABA and LFA mice had progressively limited access to food from 6 h/d at day 6 to 3 h/d at day 9 and until the end of experiment at day 17. A group of pair-fed mice (PF) was also compared to ABA.
On day 17, food intake was lower in ABA than LFA mice (2.0 ± 0.18 g vs. 3.0 ± 0.14 g, p < 0.001) and weight loss was more pronounced in ABA and PF compared to LFA mice (23.6 ± 1.6% and 24.7 ± 0.7% vs. 16.5 ± 1.2%; p < 0.05). Colonic histology showed decreased thickness of the muscularis layer in ABA compared to LFA mice (p < 0.05). Colonic permeability was increased in both ABA and PF compared to LFA mice (p < 0.05) but jejunal paracellular permeability was not affected. Expression of claudin-1 in the colon was lower in the ABA than the LFA group (p < 0.05), whereas occludin expression remained unaffected.
Increased colonic permeability and histological alterations found in ABA mice suggest that intestinal barrier dysfunction may also occur in anorexia nervosa. The role of these alterations in the pathophysiology of anorexia nervosa should be further evaluated.
神经性厌食症是一种严重的进食障碍，常导致营养不良和恶病质，但它的病理生理学仍未得到明确界定。神经性厌食症期间的慢性食物限制可能导致肠道屏障功能障碍，这可能导致疾病的发展及其并发症。在这里，我们描述了活动限制型厌食症（ABA）小鼠的肠道屏障功能，ABA 是神经性厌食症的动物模型。
雄性 C57Bl/6 ABA 或限制进食（LFA）小鼠分别置于有或无活动轮的笼子中。适应 5 天后，ABA 和 LFA 小鼠的食物摄入量逐渐从第 6 天的 6 小时/天减少到第 9 天的 3 小时/天，并持续到第 17 天实验结束。还将一组配对喂养（PF）小鼠与 ABA 进行比较。
第 17 天，ABA 组的食物摄入量低于 LFA 组（2.0±0.18 g 比 3.0±0.14 g，p<0.001），ABA 和 PF 组的体重减轻比 LFA 组更为明显（23.6±1.6%和 24.7±0.7%比 16.5±1.2%；p<0.05）。结肠组织学显示，ABA 组的肌层厚度较 LFA 组减少（p<0.05）。ABA 和 PF 组的结肠通透性均高于 LFA 组（p<0.05），但空肠旁通透性不受影响。结肠中 Claudin-1 的表达在 ABA 组低于 LFA 组（p<0.05），而 Occludin 的表达不受影响。
ABA 小鼠中发现的结肠通透性增加和组织学改变表明肠道屏障功能障碍也可能发生在神经性厌食症中。这些改变在神经性厌食症的病理生理学中的作用应进一步评估。
