No abstract

Adiponectin plays a protective role in caerulein-induced AP in HFD-fed mice.

AIM:To investigate the causal relationship between hypoadiponectinemia and colorectal carcinogenesis in in vivo experimental model, and to determine the contribution of adiponectin deficiency to colorectal cancer development and proliferation. METHODS: We examined the influence of adiponectin deficiency on colorectal carcinogenesis induced by the administration of azoxymethane (AOM) (7.5 mg/kg, intraperitoneal injection once a week for 8 wk), by using adiponectin-knockout (KO) mice. RESULTS: At 53 wk after the first AOM treatment, KO mice developed larger and histologically more progressive colorectal tumors with greater frequency compared with wild-type (WT) mice, although the tumor incidence was not different between WT and KO mice. KO mice showed increased cell proliferation of colorectal tumor cells, which correlated with the expression levels of cyclooxygenase-2 (COX-2) in the colorectal tumors. In addition, KO mice showed higher incidence and frequency of liver tumors after AOM treatment. Thirteen percent of WT mice developed liver tumors, and these WT mice had only a single tumor. In contrast, 50% of KO mice developed liver tumors, and 58% of these KO mice had multiple tumors. CONCLUSION: Adiponectin deficiency enhances colorectal carcinogenesis and liver tumor formation induced by AOM in mice. This study strongly suggests that hypoadiponectinemia could be involved in the pathogenesis for colorectal cancer and liver tumor in human subjects.

Intestinal epithelial cells undergo rapid turnover and exfoliation especially at the villus tips. This process is modulated by various nutrients especially fat. Apoptosis is one of the important regulatory mechanisms of this turnover. Therefore, identification of the factors that control epithelial cell apoptosis should help us understand the mechanism of intestinal mucosal turnover. Here, we report the identification of a novel small intestine-specific member of the Ly-6 family, intectin, by signal sequence trap method. Intectin mRNA expression was exclusively identified in the intestine and localized at the villus tips of intestinal mucosa, which is known to undergo apoptosis. Intectin mRNA expression was modulated by nutrition. Intestinal epithelial cells expressing intectin were more sensitive to palmitate-induced apoptosis, compared with control intestinal epithelial cells, and such effect was accompanied by increased activity of caspase-3. Intectin expression also reduced cell-cell adhesion of intestinal epithelial cells.Intestinal epithelial cells originate from stem cells at the base of the crypt and migrate along the crypt-villus axis toward the intestinal lumen. When intestinal epithelial cells reach the luminal surface at the villus tips, they finally exfoliate into the lumen, and their cell cycle is terminated with a life span of only 3-5 days (1, 2). This constant and rapid turnover of intestinal mucosa is essential for maximal nutrient absorption, adaptation to changes in diet, and repair of mucosal injury (3).Apoptosis plays an important role in maintaining the physiological integrity of many tissues. In the intestine, apoptosis is a key regulator for the turnover of intestinal mucosa, and apoptotic intestinal epithelial cells have been detected at the villus tips of the small intestine and the colonic luminal surface (4 -6). However, the one or more underlying mechanisms of this process have not been elucidated. In this regard, it is important to identify the factors that control intestinal epithelial cell apoptosis to understand the mechanism of intestinal mucosal turnover.The present study was designed to identify a small intestinederived protein or secretory protein modulated nutritionally that is involved in the control of intestinal epithelial cell apoptosis. Using the efficient signal sequence trap (SST) 1 method (7), we identified a novel small intestine-specific GPI-anchored protein, intectin, which showed distinct localization at the villus tips of intestinal mucosa and accelerated fatty acid-induced apoptosis of intestinal epithelial cells. EXPERIMENTAL PROCEDURESCloning of Intectin cDNA-Poly(A) ϩ RNAs were extracted from the small intestinal epithelium of C57BL/6J mice under three feeding conditions; ad libitum, 24-h fasting, and 24-h fasting followed by 24-h feeding, and from the small intestinal epithelium of ad libitum-fed db/db mice. Equal amount of poly(A) ϩ RNA from each group was pooled and used as the template to synthesize complementary DNA (cDNA). To selectively clone the gen...