P020 Effects of Anti-TNF Treatment on Browning of Mesenteric Adipose Tissue with Crohn's Disease

Abstract

Abstract Background Crohn's disease (CD) is characterized by the expansion of mesenteric fat, known as creeping fat (CrF), to the inflamed segments of the intestine. Our group observed that CrF showed a conversion to beige tissue, a phenomenon known as "Browning", characterized by an elevated gene expression of thermogenin (UCP-1), the gene characteristic of browning1. A recent study also showed that when browning was induced in mice in a TNBS colitis model, mesenteric hypertrophy improved and inflammation in adipose tissue was reduced2. The aim of this study is to assess whether the administration of anti-TNF biologic treatment (infliximab) in patients with CD is related to the increase in adipose beige tissue in the CrF. Methods Immunohistochemistry staining of UCP-1 was conducted on CrF samples from CD patients receiving anti-TNF treatment (≥6 months) and anti-TNF-naïve patients. Additionally, we analysed the gene expression of beige adipose markers in CrF from CD patients treated with anti-TNF drugs, comparing them to those untreated. UCP-1 gene expression was also studied in adipose-stem cells isolated from CrF. Ongoing experiments involve treating adipose stem cells with infliximab (10ug/ml) for 24 hours to assess the potential conversion of white to beige adipose tissue. Results The study revealed a significant increase in UCP-1 staining in CrF samples among patients receiving anti-TNF treatment compared to anti-TNF-naïve CD patients (Fig 1.A). This trend was consistently observed in mesenteric CrF tissue. Beige markers TMEM26 and CPTB1 exhibited significant increases in anti-TNF-treated CrF, and other beige tissue markers showed a notable trend (Fig 1.B). Adipose stem cells displayed a significant increase in UCP-1 gene expression in anti-TNF-treated CrF compared to untreated patients (Fig 1.C). Exciting preliminary data suggest that infliximab treatment increases UCP-1 and the anti-inflammatory cytokine IL-4 gene expression in adipose-stem cells from active CD patients (Fig 1.D). This novel data implies a direct relationship between anti-TNF treatment and heightened browning in white adipose tissue of CD patients. Conclusion This study reveals a notable increase in UCP-1 gene expression in adipose tissue CrF of CD patients undergoing anti-TNF treatment. The findings suggest that anti-TNF therapy may trigger the transformation of white adipose tissue into the "beige" type, potentially mitigating inflammation. Browning CrF presents a promising therapeutic avenue for CD management, warranting further investigation. Ref: 1. D. Monfort-Ferré et al. J Crohn Colitis., 2022;16(10):1571–83, 2. Zuo L et al. J Crohn Colitis. 2023 21;17(8):1179-1192.