Link between obesity and cancer: role of triglyceride/free fatty acid cycling.

Obesity has long been suspected to be a risk factor for cancer. The relationship between body fat deposition and the pathogenesis of cancer has been the subject of many studies, however, no clear consensus has emerged linking these two biological processes. Recent epidemiological studies showed a strong association between cancer-related deaths and increased body-mass index. In fact, obesity has been identified as a cause for oesophageal, colon, uterine, kidney and post-menopausal breast cancers and also as a significant risk factor for the cancers of prostate, pancreas and non-Hodgkin lymphoma. Approximately 16-20% of cancer deaths in women and 14% of cancer deaths in men were found to be due to obesity. It is also recognized that there is a positive relationship between type-2 diabetes associated hyperinsulinemia and cancer incidence. Though the recent annual report in US finds that the incidence and mortality rates for many cancers have dropped in 2003 since 1975, this decline is mostly due to a substantial decrease in tobacco use among men. However, during the same period the rise in the prevalence of obesity might have contributed to the increased risk and incidence of prostate, liver, kidney, oesophageal and breast cancers. Whether the elevated cancer risk in obesity arises from similar modulation of parallel signaling/metabolic pathways during adipogenesis and oncogenesis has not been hitherto addressed. In this Review we would like to bring out the similarities between adipogenesis and oncogenesis and how this relationship at molecular level may be relevant for the development of effective therapeutics for obesity, diabetes and cancer. While adipogenesis is the process of formation of mature adipocytes or fat cells under normal physiological conditions, oncogenesis is a pathological process, which results in the uncontrolled growth of cells leading to cancer. Though, both these processes at surface seem to be totally different, we believe that there are important common denominators for these processes that need to be recognized. We will discuss the role of two such underlying factors - (1) malonyl-CoA, an important regulator of fatty acid metabolism and (2) triglyceride/free fatty acid (TG/FFA) cycling which is central to the generation of multiple signals for controlling various metabolic, physiological and signaling pathways in the cell.