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.

Fig. 1

Transformation model of CRC. Ingoing arrows concern oncogenic effectors that are turned on in the cancer progression. Outgoing arrows highlight tumour suppressor factors that become inactivated in colon cancer

Fig. 2

Schematic diagram of biochemical features of obesity. Up and down arrows denote up- or downregulation respectively