Poster Session I - A161 G0S2 PROTEIN REGULATES COLON INFLAMMATION AND COLORECTAL CANCER THROUGH PRODUCTION OF BRANCHED-CHAIN FATTY ACIDS

Background Branched-chain fatty acid esters of hydroxy fatty acids (FAHFAs) are a novel class of endogenous anti-inflammatory and anti-colitis lipids. It has recently been discovered that adipose triglyceride lipase (ATGL), a key enzyme in triglyceride lipolysis, catalyzes the synthesis of FAHFAs. The G0S2 protein (G0/G1 switch gene 2) functions as an endogenous inhibitor of triglyceride breakdown by binding to ATGL. However, how the regulation of FAHFA production by the ATGL/G0S2 axis affects colon inflammation and colorectal cancer progression has never been addressed. Aims This study aims to investigate how the ATGL/G0S2 axis regulates the production of anti-inflammatory FAHFAs and how this regulation impacts colon inflammation and colorectal cancer. Methods We have previously derived a G0s2 knockout (KO) mouse and we measured FAHFA levels in vivo by Liquid Chromatography-Mass Spectrometry (LC-MS). To assess the impact of FAHFAs on inflammation, we treated the G0s2 KO and wild-type controls with DSS to induce experimental colitis. Additionally, we used AOM/DSS-induced colorectal tumorigenesis and ApcMin/+-driven intestinal cancer model to examine how G0S2 affects tumour progression. Results We found that G0s2 KO mice are more resistant to DSS induced colitis and both AOM/DSS induced and ApcMin/+ driven tumorigenesi. Conclusions Our data suggest that the ATGL/G0S2 axis can affect colon inflammation and colorectal cancer through ATGL-mediated FAHFA production.