Insulin, leptin, and adiponectin receptors in colon: regulation relative to differing body adiposity independent of diet and in response to dimethylhydrazine

Abstract

Obesity has recently become a focus of research to elucidate diet and lifestyle factors as important risk factors for colon cancer. Altered levels of insulin, leptin, and adiponectin have been identified as potential candidates increasing colon cancer risk within the prevailing obesogenic environment. There has been considerable research to characterize signaling via these hormones in the brain, liver, and adipose tissue; however, very little is known of their emerging role in peripheral signaling, particularly in epithelial tissues. This study profiles insulin, leptin, and adipokine receptors in the rat colon, revealing novel microanatomical location of these receptors and thereby supporting a potential role in regulating colonic tissue. Potential involvement of insulin, leptin, and adiponectin receptors in increased risk of colon cancer was investigated using Sprague-Dawley rats, either resistant or susceptible to diet-induced obesity. Regulation of insulin, leptin, and adiponectin receptors as a consequence of differing levels of adiposity was assessed regionally in the colon in response to treatment with the chemical carcinogen 1,2-dimethylhydrazine (DMH). However, significantly increased fat mass, increased levels of plasma insulin, leptin, and triglycerides, previously associated with an increased risk of colon cancer, were not associated with promotion of precancerous lesions in the experimental rats or deregulation of insulin, leptin, or adiponectin receptors. These findings do not support a direct link between the deregulation of insulin and adipokine levels observed in obese rats and an increased risk of colon carcinogenesis.

Impact of Body Mass Index on the Risk of Colorectal Adenoma in a Metabolically Healthy Population

“…Altered adipokine secretion from the adipose tissue, such as leptin and adiponectin, is considered a potential mediator for obesity-related colon cancer (35)(36)(37)(38). Colon epithelial cells express adiponectin and leptin receptors, supporting the potential of adiponectin and leptin to influence regulation of cellular processes within the colon (39). A recent study showed that adiponectin directly inhibits colon cancer cell proliferation (40).…”

Effects of diet-induced obesity on colitis-associated colon tumor formation in A/J mice

“…5 Evidence for a positive relationship between circulating insulin concentration and colon cancer risk exists, and a recent meta-analysis showed an increased risk of colorectal cancer with high C-peptide/insulin levels (relative risk ¼ 1.31, 95% confidence interval: 1.13-1.61) in men. 6 Chronically elevated concentrations of insulin decrease insulin-like growth factor-1 binding protein (IGFBP-1) levels, which, in turn, increase the circulating concentration of IGF-1.…”

Obesity enhances gastrointestinal tumorigenesis in Apc-mutant mice

“…[1][2][3] A putative association between obesity and colon cancer has been explored experimentally using chemical carcinogens administered to obese rodents. 4,5 The main objective of this study was to generate a new mouse line that displays both obesity and intestinal tumorigenesis. To this end, we have generated double mutant C57BLKS-mLepr db/db ; Apc 1638N/ þ mice, henceforth referred to as Lepr db/db ; Apc 1638N/ þ ; Lepr db/db mice carry a missense mutation resulting in premature termination of the intracellular domain of the long form of the leptin receptor (Ob-Rb, ref.…”