Molecular mechanisms linking adipokines to obesity-related colon cancer: focus on leptin

Abstract

Obesity is linked to increased risk of colon cancer, currently the third most common cancer. Consequently rising levels of obesity worldwide are likely to significantly impact on obesityrelated colon cancers in the decades to come. Understanding the molecular mechanisms whereby obesity increases colon cancer risk is thus a focus for research to inform strategies to prevent the increasing trend in obesity-related cancers. This review will consider research on deregulation of adipokine signalling, a consequence of altered adipokine hormone secretion from excess adipose tissue, with a focus on leptin, which has been studied extensively as a potential mediator of obesity-related colon cancer. Numerous investigations using colon cell lines in vitro, in vivo studies in rodents and investigations of colon cancer patients illuminate the complexity of the interactions of leptin with colon tissues via leptin receptors expressed by the colon epithelium. Although evidence indicates a role for leptin in proliferation of colon epithelial cells in vitro, this has been contradicted by studies in rodent models. However, recent studies have indicated that leptin may influence inflammatory mediators linked with colon cancer and also promote cell growth dependent on genotype and is implicated in growth promotion of colon cancer cells. Studies in human cancer patients indicate that there may be different tumour sub-types with varying levels of leptin receptor expression, indicating the potential for leptin to induce variable responses in the different tumour types. These studies have provided insights into the complex interplay of adipokines with responsive tissues prone to obesity-related colon cancer. Deregulation of adipokine signalling via adipokine receptors located in the colon appears to be a significant factor in obesity-related colon cancer. Molecular profiling of colon tumours will be a useful tool in future strategies to characterise the influence that adipokines may have on tumour development and subsequent therapeutic intervention. Study of the molecular mechanisms linking obesity with cancer also supports recommendations to maintain a normal body weight to reduce the risk of colon cancer.

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

“…Adipose tissue is an important endocrine organ secreting numerous adipokines consisting of hormones, cytokines, and other signaling molecules that play roles in energy balance, inflammation, insulin sensitivity, and angiogenesis (32)(33)(34). 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).…”

Association of Leptin Receptor Lys109Arg and Gln223Arg Polymorphisms with Increased Risk of Clear Cell Renal Cell Carcinoma

“…The potential associations of these variants with cancer have been evaluated in different cancers, included cancers of breast Dallal et al, 2013), colorectum (Drew, 2012;Liu et al, 2013), gastric (Kim et al, 2012), lung (Li et al, 2012) and oral (Yapijakis et al, 2009). However, the relationship between the polymorphisms of LEPR and CC-RCC is not well studied.…”

Leptin and leptin receptor expressions in prostate tumors may predict disease aggressiveness?

“…Patients with prostate cancer have elevated serum levels of leptin 16 , and this is correlated with tumor volume, histological classification, biochemical recurrence, metastasis, and disease progression, as well as an increase in mortality 6 . There is also a strong correlation between serum leptin levels and PSA 16,17 .…”