Treating fatty liver for the prevention of cardiovascular diseases
Authors: Federico Salamone, Fabio Galvano, Giovanni Li Volti
Journal: Hepatology (2010)

We read with great interest the article by Speliotes et al.,1 who have demonstrated that fatty liver is associated with the main features of metabolic syndrome (MetS) independently of visceral fat in the well-known population of the Framingham Heart Study. The study potently shows that the quantity of liver fat, as measured by multidetector computed tomography, predicts the presence of the typical glucose and lipid metabolic disturbances of MetS in an independent manner. Interestingly, the study also demonstrates that fatty liver is associated with an increase in blood pressure. Because of the cross-sectional nature of the study, in their conclusion, the authors show caution in interpreting their findings as proof of concept of the pivotal role of liver fat in the pathophysiology of cardiovascular events in MetS. Nonetheless, we suggest that their findings could have been strengthened if the authors had taken into account recent findings coming from translational research. In particular, Korenblat et al.2 first showed that insulin action in the liver, muscle, and adipose tissue is directly related to the intrahepatic triglyceride (IHTG) content in obese subjects, and these findings were further extended by Fabbrini et al.,3 who elegantly demonstrated that the IHTG content predicts the impairment of insulin action in the liver, adipose tissue, and muscle better than visceral fat. Consistently, an increase in whole-body adiposity without an increase in IHTG is not associated with augmented metabolic dysfunction.4 The aforementioned studies did not investigate the molecular pathways involved in the disturbed crosstalk between the adipose tissue, liver, and muscle, and the studies in mice provided contrasting evidence in this respect. Nevertheless, taken together, these data indicate that the treatment of fatty liver should be a main target for the prevention of cardiovascular events, which are the hallmark of MetS.5 Currently, nonalcoholic fatty liver disease is strongly divided into the categories of nonalcoholic fatty liver and nonalcoholic steatohepatitis. Nonalcoholic fatty liver is not a progressive liver disease, whereas nonalcoholic steatohepatitis is characterized by inflammatory and fibrogenic behavior and may have a cirrhotic and tumorigenic evolution. Although this classification is well justified when patients at risk for liver-related mortality are being identified, it should not lead to nonalcoholic fatty liver being considered a benign condition because it is associated with increased cardiovascular mortality and overall mortality.6 Noteworthily, the presence of fatty liver is completely ignored in the international consensus on MetS5 and in the guidelines on diabetes management from the American Diabetes Association.7 Strikingly, the decrease in IHTG with physical activity leads to a marked improvement in systemic insulin resistance independently of the decrease in visceral adipose tissue.8 Thus, we suggest that fatty liver management should be a main goal in the treatment of MetS. Finally, we agree with the authors' conclusions that prospective clinical studies will further clarify whether IHTG measurement can be a prompt predictor of the cardiometabolic risk. If this is the case, shall we call it fatty liver syndrome? Federico Salamone M.D.*, Fabio Galvano Ph.D. , Giovanni Li Volti M.D., Ph.D. , * Department of Internal Medicine, University of Catania, Catania, Italy, Department of Biological Chemistry, Medical Chemistry, and Molecular Biology, University of Catania, Catania, Italy.