Low dose dietary resveratrol interacts with adiponectin to attenuate obesity‐associated colorectal tumorigenesis

Obesity is associated with a decrease in the anti‐inflammatory hormone, adiponectin (Adn), and a subsequent increase in pro‐inflammatory cytokine release into the circulation. These changes contribute to initiation and propagation of colon tumorigenesis. Resveratrol has been effective at attenuation of colon cancer and has been shown to increase Adn production in adipocytes. Thus, we hypothesized that resveratrol interacts with Adn in obesity to inhibit colorectal tumorigenesis. To investigate this we induced tumorigenesis in Adn knockout (KO) and wild type (Wt) C57BL/6 mice through azoxymethane injection (10 mg/kg body weight) followed by 1% dextran sodium sulfate in drinking water for 5 days. Concurrently, mice were fed one of two ad libitum obesigenic diets for 14 weeks: high fat lard (HFL) and HFL with 20mg/kg diet resveratrol (HFL+R). Wt mice gained more weight, had higher percent fat mass, and lower lean mass than KO, and HFL+R diet tended to attenuate this response in male Wt mice. There was a strong tendency for an interaction between genotype and diet whereby HFL+R diet increased lesion development in KO male mice, and HFL diet decreased lesion formation in WT male mice. HFL+R also tended to decrease serum insulin and interleukin 6 in Wt mice. Thus, HFL+R diet improved overall heath of obese Wt male but not KO male mice. Supported by grant 2008‐34115‐19372 to the Nutrition and Wellness Research Center from USDA. Grant Funding Source: Supported by grant 2008‐34115‐19372 to the Nutrition and Wellness Research Center from USDA