Molecular Nutrition, Rowett Institute of Nutrition and Health, University of Aberdeen, Bucksburn, Aberdeen, Scotland, UK.
J Cell Physiol. 2011 Aug;226(8):2123-30. doi: 10.1002/jcp.22546.
Dysregulation of leptin associated with obesity is implicated in obesity-related colon cancer, but mechanisms are elusive. Increased adiposity and elevated plasma leptin are associated with perturbed metabolism in colon and leptin receptors are expressed on colon epithelium. We hypothesise that obesity increases the sensitivity of the colon to cancer by disrupting leptin-regulated gene targets within colon tissues. PCR arrays were used to firstly identify leptin responsive genes and secondly to identify responses to leptin challenge in wild-type mice, or those lacking leptin (ob/ob). Leptin-regulated genes were localised in the colon using in situ hybridisation. IL6, IL1β and CXCL1 were up-regulated by leptin and localised to discrete cells in gut epithelium, lamina propria, muscularis and at the peritoneal serosal surface. Leptin regulates pro-inflammatory genes such as IL6, IL1β and CXCL1, and might increase the risk of colon cancer among obese individuals.
与肥胖相关的瘦素失调与肥胖相关的结肠癌有关，但机制尚不清楚。脂肪量增加和血浆瘦素水平升高与结肠代谢紊乱有关，而结肠上皮表达瘦素受体。我们假设肥胖通过破坏结肠组织内瘦素调节的基因靶点，增加了结肠对癌症的敏感性。我们首先使用 PCR 阵列来鉴定瘦素反应基因，其次鉴定野生型小鼠或缺乏瘦素（ob/ob）的小鼠对瘦素挑战的反应。使用原位杂交技术将瘦素调节的基因定位于结肠。瘦素上调了 IL6、IL1β 和 CXCL1，并定位于肠道上皮、固有层、肌层和腹膜浆膜表面的离散细胞中。瘦素调节 IL6、IL1β 和 CXCL1 等促炎基因，可能会增加肥胖人群患结肠癌的风险。
