Aberrant crypt foci (ACF), which were first discovered in mice treated
with azoxymethane (AOM) have been clearly shown to be precursor lesions of CRC and are now established as a biomarker of the risk of CRC in AOM-treated mice and rats. In humans, ACF are considered as a possible biomarker of the risk of CRC (Fig. 2). Previous studies have demonstrated that individuals with CRC have a larger number of ACF than those without CRC. Recently, an association between obesity and the risk of CRC was suggested.[16, 17] We demonstrated a significant correlation between the number of dysplastic ACF and the visceral fat area (VFA), as measured on abdominal computed tomography (CT) images, and also a significant inverse correlation MK-2206 in vivo between the former and the plasma adiponectin levels (Table 1).[3, GS-1101 molecular weight 18] Several reports have suggested the existence of relationships between the risk of CRC and exercise, energy use, glycemic index, food choices, and dietary constituents.[19-21] As these factors also often influence one another, it is difficult to evaluate the relationship between any one of these factors alone and the risk of CRC; however, obesity is known to be related to many of these factors. We demonstrated the existence of a relationship between the number of ACF and the serum levels of peroxisome proliferator-activated receptor (PPAR)-γ or insulin-like
growth factor-1 in humans.[22, 23] To clarify the role of obesity and reduced plasma adiponectin levels in colorectal carcinogenesis, further studies were conducted using mouse models. We demonstrated that obesity is an important risk factor for colorectal carcinogenesis in humans using the number of ACF as a surrogate marker of CRC. Epidemiological studies have revealed that obesity, especially visceral obesity, is associated with an elevated risk of colon adenoma and CRC; in addition, the results of animal
experiments also suggest the existence of a link between obesity and CRC.[24, 25] Obesity is strongly associated with adipose tissue dysfunction and altered serum levels of adipokines, which might underlie the elevated risk of CRC associated with it. Adiponectin, also known as ACRP30 or AdipoQ, is a 30-kDa adipokine selleck chemicals composed of 247 amino acids.[27, 28] Several clinical studies in humans have reported the existence of a relationship between the plasma levels of adiponectin and the risk of CRC.[17, 29] However, there had been no animal model studies on the relationship between the serum adiponectin levels and the risk of CRC until our study carried out using adiponectin-deficient mice was published. Therefore, the mechanism underlying the promotion of colorectal carcinogenesis by adiponectin deficiency remains unclear. We investigated the effect of adiponectin in suppressing the development of CRC under the normal and high-fat diet conditions in an AOM-induced CRC model.