Obesity exacerbates experimental colitis due to the activation of the local renin-angiotensin system in the colon.

Abstract

Obesity is recognized as a risk factor for inflammatory bowel disease (IBD) and may contribute to its progression. However, the underlying mechanisms remain unclear. This study aimed to investigate the impact of high-fat diet (HFD)-induced obesity on the development of experimental colitis, with a particular focus on the role of the gut renin-angiotensin system (RAS) in this process. C57BL/6J mice were assigned to either a low-fat diet (LFD) or HFD for 10 weeks to establish an obesity model.The severity of colitis was significantly greater in obese mice compared to those fed the LFD. Additionally, obesity was associated with increased levels of IL-6, IFN-γ, and TNF-α, while simultaneously downregulating the expression of occludin proteins in the colon, leading to increased colonic permeability in the obese mice. Following colitis induction, HFD -induced obesity activated the RAS by upregulating the expression of angiotensin II receptor, angiotensinogen, and renin in the colon. Treatment with a RAS inhibitor significantly alleviated the symptoms of colitis in the obese mice. These findings suggest that HFD-induced obesity enhances intestinal mucosal barrier permeability and exacerbates mucosal inflammation through the activation of the local RAS, thereby promoting colitis.