Obesity and colorectal cancer: molecular features of adipose tissue

Abstract

The huge part of population in developed countries is overweight or obese. Obesity is often determined by body mass index (BMI) but new accurate methods and ratios have recently appeared to measure body fat or fat located in the intestines. Early diagnosis of obesity is crucial since it is considered an increasing colorectal cancer risk factor. On the one hand, colorectal cancer has been strongly associated with lifestyle factors. A diet rich in red and processed meats may increase colorectal cancer risk; however, high-fiber diets (grains, cereals and fruits) have been associated with a decreased risk of colorectal cancer. Other life-style factors associated with obesity that also increase colorectal cancer risk are physical inactivity, smoking and high alcohol intake. Cutting-edge studies reported that high-risk transformation ability of adipose tissue is due to production of different pro-inflammatory cytokines like IL-8, IL-6 or IL-2 and other enzymes like lactate dehydrogenase (LDH) and tumour necrosis factor alpha (TNFα). Furthermore, oxidative stress produces fatty-acid peroxidation whose metabolites possess very high toxicities and mutagenic properties. 4-hydroxy-2-nonenal (4-HNE) is an active compounds that upregulates prostaglandin E2 which is directly associated with high proliferative colorectal cancer. Moreover, 4-HNE deregulates cell proliferation, cell survival, differentiation, autophagy, senescence, apoptosis and necrosis via mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PIK3CA)—AKT and protein kinase C pathways. Other product of lipid peroxidation is malondialdehyde (MDA) being able to regulate insulin through WNT-pathway as well as having demonstrated its mutagenic capability. Accumulation of point mutation enables genomic evolution of colorectal cancer described in the model of Fearon and Vogelstein. In this review, we will summarize different determination methods and techniques to assess a truthfully diagnosis and we will explain some of the capabilities that performs adipocytes as the largest endocrine organ.

Melatonin-Induced Changes in Cytosolic Calcium Might be Responsible for Apoptosis Induction in Tumour Cells

“…This difference is interesting both from the theoretical and therapeutic points of view, but the mechanisms behind it are not understood. In normal cells, the products of several tumour suppressor genes counteract oxidative stress and maintain the redox balance by prevention of lipid peroxidation and oxidative damage to DNA and proteins [48]. In the absence of wild-type tumour suppressor genes, such as TP53 , cancer cells switch off several antioxidative pathways, leading to ROS accumulation [49].…”

Regulation of Autophagy-Related Protein and Cell Differentiation by High Mobility Group Box 1 Protein in Adipocytes

“…Obesity leads not only to an increase in adipose tissue mass but also to the infiltration of proinflammatory cells and secretion of inflammatory cytokines [1, 2]. Therefore, obesity is characterized by low-grade inflammation in local and systemic sites as demonstrated by robust secretion of proinflammatory cytokines, including IL-6, as well as active recruitment of leukocytes [3]. Substantial evidence supports the hypothesis indicating that inflammation may contribute to insulin resistance, which further induces a series of diseases such as diabetes, hypertension, fatty liver disease, and coronary heart disease, thereby threatening human health [4, 5].…”

Tumor SQSTM1 (p62) expression and T cells in colorectal cancer

“…[48][49][50][51][52][53] The importance of analyses of human tumor characteristics and host immunity has been increasing. 37,54 In fact, higher densities of CD3 C , CD8 C , and CD45RO C cells in colorectal cancer tissue have been associated with better prognosis, [38][39][40][41][42][43]55 suggesting antitumor effects of these T cells in the tumor microenvironment.…”