Abstract
Intestinal alkaline phosphatase (IAP) is an essential mucosal defense factor involved in the process of maintenance of gut homeostasis. We determined the effect of moderate exercise (voluntary wheel running) with or without treatment with IAP on the course of experimental murine 2,4,6-trinitrobenzenesulfonic acid (TNBS) colitis by assessing disease activity index (DAI), colonic blood flow (CBF), plasma myokine irisin levels and the colonic and adipose tissue expression of proinflammatory cytokines, markers of oxidative stress (SOD2, GPx) and adipokines in mice fed a standard diet (SD) or high-fat diet (HFD). Macroscopic and microscopic colitis in sedentary SD mice was accompanied by a significant decrease in CBF, and a significant increase in the colonic expression of tumor necrosis factor-alpha (TNF-α), IL-6, IL-1β and leptin mRNAs and decrease in the mRNA expression of adiponectin. These effects were aggravated in sedentary HFD mice but reduced in exercising animals, potentiated by concomitant treatment with IAP, especially in obese mice. Exercising HFD mice demonstrated a substantial increase in the mRNA for adiponectin and a decrease in mRNA leptin expression in intestinal mucosa and mesenteric fat as compared to sedentary animals. The expression of SOD2 and GPx mRNAs was significantly decreased in adipose tissue in HFD mice, but these effects were reversed in exercising mice with IAP administration. Our study shows for the first time that the combination of voluntary exercise and oral IAP treatment synergistically favored healing of intestinal inflammation, strengthened the antioxidant defense and ameliorated the course of experimental colitis; thus, IAP may represent a novel adjuvant therapy to alleviate inflammatory bowel disease (IBD) in humans.
Highlights
Introduction conditions of the Creative CommonsInflammatory bowel disease (IBD) comprises two major phenotypic types: Crohn’s disease (CD) and ulcerative colitis (UC), both characterized by chronic course with relapsing and remitting phase [1]
These effects obtained in the high-fat diet (HFD) mice were reversed when animals were subjected to voluntary exercise, as documented by a substantial reduction in disease activity index (DAI) accompanied by a significant increase in colonic blood flow (CBF) compared with non-exercising mice fed a HFD (p < 0.05) (Figure 1)
We documented for the first time in the present study that Intestinal alkaline phosphatase (IAP) administration combined with moderate physical activity by subjecting mice to wheel running could be a novel strategy to increase the efficacy of moderate voluntary physical activity affording protection against experimental colitis via further reduction in proinflammatory biomarkers, accelerating the healing of colonic inflammation compared with moderate exercise alone
Summary
Inflammatory bowel disease (IBD) comprises two major phenotypic types: Crohn’s disease (CD) and ulcerative colitis (UC), both characterized by chronic course with relapsing and remitting phase [1]. Antioxidants 2021, 10, 240 and rectum, whereas Crohn’s disease can occur in any part of the gastrointestinal tract. The precise etiology of IBDs remains unknown, it has been revealed that the combination of genetic and environmental factors promotes epithelial barrier dysfunction, which in turn enables the gut microbiome to penetrate intestinal mucosa, leading to the disturbance of the mucosal immune system and subsequent chronic inflammation [2,3,4]. Abnormal hypertrophy of mesenteric white adipose tissue (mWAT) is recognized as a characteristic feature of Crohn’s disease and leads to fat wrapping, described as the expansion of fat from the mesentery to partially cover the small and large intestines [6] The changes in gut microbiota, considered as a crucial environmental factor in IBD, are thought to result from novel diet patterns, which is consistent with the observation that the prevalence of IBD is increasing steadily in Western countries and newly industrializing countries, possibly because of the westernization of lifestyle associated with higher consumption of processed food, fat and refined sugar as well as with physical inactivity [5].
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