Adiponectin confers protection from acute colitis and restricts a B cell immune response

Abstract

Adiponectin demonstrates beneficial effects in various metabolic diseases, including diabetes, and in bowel cancer. Recent data also suggest a protective role in colitis. However, the precise molecular mechanisms by which adiponectin and its receptors modulate colitis and the nature of the adaptive immune response in murine models are yet to be elucidated. Adiponectin knock-out mice were orally administered dextran sulfate sodium for 7 days and were compared with wild-type mice. The severity of disease was analyzed histopathologically and through cytokine profiling. HCT116 colonic epithelial cells were employed to analyze the effects of adiponectin and AdipoR1 interactions in colonic injury following dextran sulfate sodium treatment. Adiponectin knock-out mice receiving dextran sulfate sodium exhibited severe colitis, had greater inflammatory cell infiltration, and an increased presence of activated B cells compared with controls. This was accompanied by an exaggerated proinflammatory cytokine profile and increased STAT3 signaling. Adiponectin knock-out mouse colons had markedly reduced proliferation and increased epithelial apoptosis and cellular stress., adiponectin reduced apoptotic, anti-proliferative, and stress signals and restored STAT3 signaling. Following the abrogation of AdipoR1 , these protective effects of adiponectin were abolished. In summary, adiponectin maintains intestinal homeostasis and protects against murine colitis through interactions with its receptor AdipoR1 and by modulating adaptive immunity.

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

“…Furthermore, leptin expression is elevated and adiponectin decreased in adipose tissue in rats with colitis fed with a normal diet, and this effect is markedly enhanced in rats fed with an HFD diet. This observation is further supported in studies in mice because the increased leptin and decreased adiponectin plasma levels and elevated expression of leptin and decreased adiponectin expression are recorded in adipose tissue, along with a disease exacerbation in mice fed with an HFD diet [4,182] (Table 3) Interestingly, adiponectin-knockout (APN-KO) mice present as more severe in comparison to WT mice [207][208][209]. Adenovirus-mediated supplementation of APN significantly attenuates the severity of colitis in both APN-KO and WT mice [207,210].…”

“…Obeid et al [209] 2017 DSS-induced colitis in APN-KO mice APN-KO mice which have shown an aggravation of DSS-induced colitis have a greater inflammatory cell infiltration and higher presence of activated B cells in comparison to controls, accompanied by an elevated proinflammatory cytokine profile production.…”

Hydroxyproline Attenuates Dextran Sulfate Sodium‐Induced Colitis in Mice: Involvment of the NF‐κB Signaling and Oxidative Stress

“…Administration of DSS for 6 consecutive days led to colitis as evidenced by body weight loss, diarrhea, shortening of the colon, and histopathological alterations, which was greatly ameliorated by Hyp. It has been reported that the overactivation of inflammatory response is a critical mediator associated with the onset of colitis . The concentrations of Hyp in the serum or colonic tissues were greater in Hyp supplementation and Hyp plus DSS co‐treatment groups as compared with that of controls.…”

Bioactive Factors in Human Breast Milk Attenuate Intestinal Inflammation during Early Life

“…Interestingly, adiponectin-deficient mice exhibited more severe colitis, decreased intestinal epithelial proliferation, increased apoptosis and cellular stress when induced with dextran sulfate sodium (DSS). This colitis was reversed in vitro when adiponectin was present [100]. However, in vivo models have suggested conflicting results and require further study.…”