MAGL-2-AG/CB1轴在肥胖介导大肠癌易感相关性中的作用

Increasing epidemiology studies demonstrated obesity and colorectal cancer have a significant association. The primary cause of obesity may directed by abnormal lipid metabolism, which may due to the lipase during the progress. Monoacyglycerol lipase has long been known for its participation in the breakdown of adipose triacylglycerol (TAG) stores, a key feature of metabolic homeostasis that, by providing tissues with free fatty acid (FFA) fuel, allows adaption to glucose deprivation periods and until it is recently reported that it is highly expressed in aggressive human cancer cells and primary tumors, where it regulates a fatty acid network enriched in oncogenic signaling lipids that promotes migration, invasion, survival. 2-Arachidonoylglycerol is an ester formed from the omega-6 fatty acid arachidonic acid and glycerol and it is hydrolyzed in vitro by monoacylglycerol lipase (MAGL), which is responsible for ~85% of this activity. And it is an endocannabinoid, an endogenous agonist of the CB1 receptor. The proteins control several biological functions, including food intake in animals and cell proliferation and apoptosis in cancer cells. Indeed, recent evidence indicates that endocannabinoids influence the intracellular events controlling the proliferation of numerous types of cancer cells, thereby leading to both in vitro and in vivo antitumor effects. So we hypothesized that the MAGL-2-AG/CB1 axis play a pivotal role in promotion of colorectal cancer mediated by obesity. Then the effect of MAGL-2-AG/CB1 signal pathway in adipocytes and colorectal cancer cells were compared in order to explore the susceptibility to colorectal cancer mediated by obese, which will provide a new sight in the correlation between obesity and colorectal cancer.

流行病学研究表明，肥胖与大肠癌的患病率有明显的相关性。而脂肪代谢的紊乱是导致肥胖的一个直接原因，代谢通路中酶的活性异常则直接导致脂肪代谢的紊乱。单酰基甘油脂肪酶（MAGL）是脂肪分解代谢中的一个重要的脂肪酶，近来研究表明，MAGL在很多侵袭性肿瘤细胞中均表达增高，它通过调节脂质信号分子，在许多肿瘤细胞的进展中有重要的调节作用。 而他的变化直接影响着内大麻素2-AG的水平，同时2-AG/CB1信号通路的激活在大肠癌的进展中有一定的促进作用。由此我们推断MAGL-2-AG/CB1轴在肥胖介导大肠癌进展中起到不可忽视的作用，而本课题组将通过对脂肪细胞及大肠癌细胞中MAGL-2-AG/CB1轴作用进行比较，探索MAGL在肥胖介导大肠癌中作用及其机制，为肥胖介导的大肠癌提供理论基础。

流行病学研究表明，肥胖与大肠癌的患病率有明显的相关性。而脂肪代谢的紊乱是导致肥胖的一个直接原因，代谢通路中酶的活性异常则直接导致脂肪代谢的紊乱。单酰基甘油脂肪酶（MAGL）是脂肪分解代谢中的一个重要的脂肪酶，近来研究表明，MAGL 在很多侵袭性肿瘤细胞中均表达增高，它通过调节脂质信号分子，在许多肿瘤细胞的进展中有重要的调节作用。 而他的变化直接影响着内大麻素 2-AG 的水平，同时 2-AG/CB1 信号通路的激活在大肠癌的进展中有一定的促进作用。由此本课题通过验证 MAGL-2-AG/CB1 轴在肥胖介导大肠癌进展中的作用，探索脂肪细胞及大肠癌细胞中 MAGL-2-AG/CB1轴作用，挖掘 MAGL 在肥胖介导大肠癌中的潜在机制，为肥胖介导的大肠癌提供理论基础。为广大肥胖患者带来早期预防，早期筛查的可能。