Adiponectin suppresses colorectal carcinogenesis under the high-fat diet condition.

The effect of adiponectin on colorectal carcinogenesis has been proposed but not fully investigated. We investigated the effect of adiponectin deficiency on the development of colorectal cancer. We generated three types of gene-deficient mice (adiponectin-deficient, adiponectin receptor 1-deficient, and adiponectin receptor 2-deficient) and investigated chemical-induced colon polyp formation and cell proliferation in colon epithelium. Western blot analysis was performed to elucidate the mechanism which affected colorectal carcinogenesis by adiponectin deficiency. The numbers of colon polyps were significantly increased in adiponectin-deficient mice compared with wild-type mice fed a high-fat diet. However, no difference was observed between wild-type and adiponectin-deficient mice fed a basal diet. A significant increase in cell proliferative activity was also observed in the colonic epithelium of the adiponectin-deficient mice when compared with wild-type mice fed a high-fat diet; however, no difference was observed between wild-type and adiponectin-deficient mice fed a basal diet. Similarly, an increase in epithelial cell proliferation was observed in adiponectin receptor 1-deficient mice, but not in adiponectin receptor 2-deficient mice. Western blot analysis revealed activation of mammalian target of rapamycin, p70 S6 kinase, S6 protein and inactivation of AMP-activated protein kinase in the colon epithelium of adiponectin-deficient mice fed with high-fat diet. Adiponectin suppresses colonic epithelial proliferation via inhibition of the mammalian target of the rapamycin pathway under a high-fat diet, but not under a basal diet. These studies indicate a novel mechanism of suppression of colorectal carcinogenesis induced by a Western-style high-fat diet.

脂联素对结直肠癌发生的影响已被提出，但尚未得到充分研究。我们研究了脂联素缺乏对结直肠癌发展的影响。 我们培育了三种基因缺陷型小鼠（脂联素缺陷型、脂联素受体1缺陷型和脂联素受体2缺陷型），并研究了化学诱导的结肠息肉形成以及结肠上皮细胞的增殖情况。进行了蛋白质印迹分析以阐明脂联素缺乏影响结直肠癌发生的机制。 与喂食高脂肪饮食的野生型小鼠相比，脂联素缺陷型小鼠的结肠息肉数量显著增加。然而，喂食基础饮食的野生型小鼠和脂联素缺陷型小鼠之间未观察到差异。与喂食高脂肪饮食的野生型小鼠相比，脂联素缺陷型小鼠的结肠上皮细胞增殖活性也显著增加；但喂食基础饮食的野生型小鼠和脂联素缺陷型小鼠之间未观察到差异。同样，脂联素受体1缺陷型小鼠的上皮细胞增殖增加，但脂联素受体2缺陷型小鼠未出现这种情况。蛋白质印迹分析显示，喂食高脂肪饮食的脂联素缺陷型小鼠的结肠上皮中，哺乳动物雷帕霉素靶蛋白、p70 S6激酶、S6蛋白被激活，而腺苷酸活化蛋白激酶失活。 在高脂肪饮食下，脂联素通过抑制哺乳动物雷帕霉素靶蛋白通路抑制结肠上皮增殖，但在基础饮食下则无此作用。这些研究表明了一种西式高脂肪饮食诱导的结直肠癌发生受抑制的新机制。