Sex, fat and infections: The molecular pathogenesis of hepatocellular carcinoma and inflammation linked cancer


Session type:

Michael Karin
UC San Diego, La Jolla, United States


Excessive caloric intake, especially in the form of fats, and ensuing obesity are some of the most common and serious “plagues” associated with modern life style, being responsible for the obesity epidemic that afflicts both affluent and rapidly developing societies. In addition to metabolic abnormalities, such as insulin resistance, glucose intolerance and hyperlipidemia that greatly increase the risk of type II diabetes and atherosclerosis, obesity and excessive caloric intake result in a substantial increase in cancer risk and are responsible for at least 90,000 cancer related deaths per year in the US. Of all cancers, obesity and overweight have the most pronounced effect on hepatocellular carcinoma (HCC), the most common and aggressive form of liver cancer. Recent epidemiological studies indicate that obesity can result in up to a 4.5-fold increase in HCC risk. Despite these astounding epidemiological findings and the huge toll conferred by the obesity epidemic on cancer-related morbidity and mortality, as well as on health care costs, mechanistic understanding of the effects of obesity on tumor development and progression is lacking. This deficiency is due to the absence of genetically-dissectible mouse models of cancer in which excess caloric intake and obesity enhance tumor development. To fill this void and address one of the major public health problems in the US and elsewhere, we have developed a mouse model in which high fat diet-induced obesity results in a marked enhancement of HCC development and progression. We will use this model to identify the mechanisms by which excessive caloric intake and obesity, acting through signaling networks that are involved in nutrient sensing and the control of energy metabolism, increase cancer risk and enhance tumor development.