Hursting Stephen D, Nunez Nomeli P, Varticovski Lyuba, Vinson Charles
Division of Nutritional Sciences, University of Texas, Austin, Texas, USA.
Cancer Res. 2007 Mar 15;67(6):2391-3. doi: 10.1158/0008-5472.CAN-06-4237.
Current dogma suggests that the positive correlation between obesity and cancer is driven by white adipose tissue that accompanies obesity, possibly through excess secretion of adipokines. Recent studies in fatless A-Zip/F1 mice, which have undetectable adipokine levels but display accelerated tumor formation, suggest that adipokines are not required for the enhanced tumor development. The A-Zip/F-1 mice are also diabetic and display elevated circulating levels of other factors frequently associated with obesity (insulin, insulin-like growth factor-1, and proinflammatory cytokines) and activation of several signaling pathways associated with carcinogenesis. In view of this information, the risk factors underlying the obesity-cancer link need to be revisited. We postulate that the pathways associated with insulin resistance and inflammation, rather than adipocyte-derived factors, may represent key prevention and therapeutic targets for disrupting the obesity-cancer link.
当前的理论认为，肥胖与癌症之间的正相关是由伴随肥胖出现的白色脂肪组织驱动的，可能是通过脂肪因子的过度分泌。最近对无脂肪的A-Zip/F1小鼠的研究表明，脂肪因子并非增强肿瘤发展所必需，这些小鼠的脂肪因子水平无法检测到，但肿瘤形成加速。A-Zip/F-1小鼠也是糖尿病模型，其循环中其他经常与肥胖相关的因子（胰岛素、胰岛素样生长因子-1和促炎细胞因子）水平升高，并且与致癌作用相关的几种信号通路被激活。鉴于这些信息，肥胖与癌症关联背后的风险因素需要重新审视。我们推测，与胰岛素抵抗和炎症相关的通路，而非脂肪细胞衍生的因子，可能是破坏肥胖与癌症关联的关键预防和治疗靶点。
