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Obesity and inflammation play a vital role in colorectal cancer (CRC). Antiobesity agents may be beneficial for CRC prevention. Celastrol is a triterpene bioactive compound derived from Tripterygium wilfordii (TW) plant, which possesses antiobesity and anti-inflammatory properties. In the present study, we tested celastrol for its intestinal tumor inhibitory efficacy, modulation of intestinal microbiome, induction of UCP-1 in inguinal fat, and inflammation under obese conditions using APC^Min/+ mouse model. For efficacy study, six-week-old male and female C57BL/6J-APC^Min/+ mice (10 mice/group/gender) were fed high-fat diets (HFD; 60% Kcal fat) containing 0 and 150 ppm celastrol and a group of mice with a low-fat diet (LFD; 10% Kca fat) for 11 weeks. At termination, intestinal tumors were evaluated histologically and serum was assayed for fasting glucose, uric acid, liver enzymes (ALT, AST), triglycerides and …