Department of Food and Nutrition, Sookmyung Women's University, Seoul, Korea.
Int J Obes (Lond). 2012 Feb;36(2):273-80. doi: 10.1038/ijo.2011.83. Epub 2011 Apr 19.
Studies have indicated that obesity is associated with a higher risk of colorectal cancer. This study was performed to determine the effect of diet-induced obesity on the formation of azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon tumors and to identify adiposity-related mechanisms.
Male A/J mice were placed on either a high-fat diet (HFD; 45% of total calories from fat) or a normal diet (ND; 15% of calories from fat) for 12 weeks. To induce colon tumors, AOM was administered at a dose of 10 mg/kg body weight, followed by two cycles of DSS supply.
Study results indicated that the HFD group had twofold higher numbers of colonic tumors, as compared with the ND group. The HFD group also had significantly increased body weight and epididymal fat weight, which were associated with increases of serum insulin, insulin-like growth factor-1, leptin, epididymal fat pad leptin mRNA and colonic leptin receptor (Ob-R) mRNA. Animals on HFD showed higher expressions of Ob-R, insulin receptor, phosphorylated Akt, phosphorylated extracellular signal-regulated kinases, Bcl-xL and Cyclin D1 proteins in the colon.
The results suggest that HFD-induced obesity facilitates colon tumor formation, possibly by regulating downstream targets of circulating adiposity-related factors via receptor-mediated signaling of the phosphatidylinositol 3-kinase/Akt pathway.
研究表明肥胖与结直肠癌风险增加有关。本研究旨在确定饮食诱导肥胖对氧化偶氮甲烷（AOM）/葡聚糖硫酸钠（DSS）诱导的结肠肿瘤形成的影响，并确定与肥胖相关的机制。
雄性 A/J 小鼠分别给予高脂肪饮食（HFD；总热量的 45%来自脂肪）或正常饮食（ND；15%的热量来自脂肪）12 周。用 10mg/kg 体重的 AOM 诱导结肠癌，然后用 DSS 供应两个周期。
研究结果表明，HFD 组的结肠肿瘤数量是 ND 组的两倍。HFD 组的体重和附睾脂肪重量也显著增加，这与血清胰岛素、胰岛素样生长因子-1、瘦素、附睾脂肪垫瘦素 mRNA 和结肠瘦素受体（Ob-R）mRNA 的增加有关。HFD 组动物的结肠中 Ob-R、胰岛素受体、磷酸化 Akt、磷酸化细胞外信号调节激酶、Bcl-xL 和 Cyclin D1 蛋白的表达水平更高。
结果表明，HFD 诱导的肥胖促进了结肠肿瘤的形成，可能是通过受体介导的磷酸肌醇 3-激酶/Akt 途径的信号转导，调节循环肥胖相关因子的下游靶标。
