Beneficial Effect of Voluntary Exercise on Experimental Colitis in Mice Fed a High-Fat Diet: The Role of Irisin, Adiponectin and Proinflammatory Biomarkers

Abstract

Inflammatory bowel diseases (IBDs) are a heterogeneous group of disorders exhibited by two major phenotypic forms: Crohn‘s disease and ulcerative colitis. Although the aetiology of IBD is unknown, several factors coming from the adipose tissue and skeletal muscles, such as cytokines, adipokines and myokines, were suggested in the pathogenesis of ulcerative colitis; however, it has not been extensively studied whether voluntary exercise can ameliorate that disorder. We explored the effect of moderate exercise (i.e., voluntary wheel running) on the disease activity index (DAI), colonic blood flow (CBF), plasma irisin and adiponectin levels and real-time PCR expression of proinflammatory markers in mesenteric fat in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS) colitis fed a high-fat diet (HFD) compared to those on a standard chow diet (SD). Macroscopic and microscopic colitis in sedentary SD mice was accompanied by a significant fall in CBF, some increase in colonic tissue weight and a significant increase in the plasma levels of tumour necrosis factor-alpha (TNF-α), IL-6, monocyte chemotactic protein 1 (MCP-1) and IL-13 (p < 0.05). In sedentary HFD mice, colonic lesions were aggravated, colonic tissue weight increased and the plasma TNF-α, IL-6, MCP-1, IL-1β and leptin levels significantly increased. Simultaneously, a significant decrease in the plasma irisin and adiponectin levels was observed in comparison with SD mice (p < 0.05). Exercise significantly decreased macroscopic and microscopic colitis, substantially increased CBF and attenuated the plasma TNF-α, IL-6, MCP-1, IL-1β and leptin levels while raising the plasma irisin and the plasma and WAT concentrations of adiponectin in HFD mice (p < 0.05). We conclude that: (1) experimental colitis is exacerbated in HFD mice, possibly due to a fall in colonic microcirculation and an increase in the plasma and mesenteric fat content of proinflammatory biomarkers; and (2) voluntary physical activity can attenuate the severity of colonic damage in mice fed a HFD through the release of protective irisin and restoration of plasma adiponectin.

Role of Obesity, Mesenteric Adipose Tissue, and Adipokines in Inflammatory Bowel Diseases

“…Numerous studies confirm that a high-fat diet (HFD) or high-fat and high-sugar diets (HF/HSD) can exacerbate experimentally induced colitis. In murine colitis models, the diet modifications are attributed to the alterations in the plasma levels of proinflammatory biomarkers and the expression of proinflammatory factors in VAT [102,108,128,[179][180][181][182][183][184][185][186][187]. It was demonstrated that the application of an HFD or HF/HSD diets and/or the development of obesity in mice increase(s) the intestinal permeability and bacterial translocation from the intestinal lumen to mesenteric fat, as well as profound changes in the microbiota [102,108,127,181,[184][185][186][187][188][189][190][191][192][193][194][195].…”

“…In murine colitis models, the diet modifications are attributed to the alterations in the plasma levels of proinflammatory biomarkers and the expression of proinflammatory factors in VAT [102,108,128,[179][180][181][182][183][184][185][186][187]. It was demonstrated that the application of an HFD or HF/HSD diets and/or the development of obesity in mice increase(s) the intestinal permeability and bacterial translocation from the intestinal lumen to mesenteric fat, as well as profound changes in the microbiota [102,108,127,181,[184][185][186][187][188][189][190][191][192][193][194][195]. HFD or HF/HSD is also associated with significantly elevated LPS levels, the reduced expression of epithelial tight junction proteins, an increased macrophage infiltration, and the increased expression of proinflammatory biomarkers in the adipose tissue [102,127,181,[184][185][186][187][188][189][190][191][192][193][196]…”

“…It was demonstrated that the application of an HFD or HF/HSD diets and/or the development of obesity in mice increase(s) the intestinal permeability and bacterial translocation from the intestinal lumen to mesenteric fat, as well as profound changes in the microbiota [102,108,127,181,[184][185][186][187][188][189][190][191][192][193][194][195]. HFD or HF/HSD is also associated with significantly elevated LPS levels, the reduced expression of epithelial tight junction proteins, an increased macrophage infiltration, and the increased expression of proinflammatory biomarkers in the adipose tissue [102,127,181,[184][185][186][187][188][189][190][191][192][193][196][197][198]. Both, the Paneth cell area and the release of antimicrobial factors by Paneth cells are reduced in HFD-fed mice [197].…”

“…Mazur-Bialy et al [184] 2017 TNBS-induced colitis in C57/BL6 mice There is increased leptin and decreased adiponectin plasma levels and elevated leptin and decreased adiponectin expression in adipose tissue, which correspond to disease exacerbation in HFD animals.…”

Adiponectin is valuable in the diagnosis of acute heart failure with renal insufficiency

“…Plasma ADPN is typically high in cats, which are overweight and functions by regulating the level of leptin (20). ADPN is considered as a useful biomarker in metabolic diseases, such as diabetes, high-fat-associated disease and dementia (21)(22)(23). In addition, it has been observed that ADPN exerts several protective functions in the peripheral tissues, including insulin sensitizing, anti-inflammatory and anti-oxidative effects, which may benefit various neurodegenerative diseases, such as Alzheimer's disease (24).…”