Fatty Liver Disease: the Hepatic Manifestation of Metabolic Syndrome

COMMENTARY

Fatty liver disease: the hepatic manifestation of metabolic syndrome

Amalia Gastaldelli

Hypertension Research (2010) 33, 546–547; doi:10.1038/hr.2010.60; published online 7 May 2010

atty liver disease (FLD) refers to a spec- Tsuneto et al. found that age, obesity (body centration.8 FLD and increased levels of hepa- F trum of liver damage ranging from sim- mass index (BMI) X25 kg mÀ2), hypertrigly- tic enzymes (i.e., alanine aminotransferase ple steatosis to nonalcoholic steatohepatitis, ceridemia and, to a lesser extent, hyperten- and g-glutamyl transpeptidase, often used as advanced fibrosis and cirrhosis. Obesity, a sion4 were among the variables that pre- markers of FLD) are used to predict the onset diet high in calories and fat, and a sedentary dicted development of FLD. Glucose intoler- of metabolic syndrome, incident CVD, and lifestyle are some of the risk factors for ance status was found to be associated even death.6,9,10 developing FLD. However, FLD is not only with an increased risk of developing FLD, Liver fat is highly correlated with all the a liver disease. It is often associated with other but the significance was lost when the data components of metabolic syndrome, inde- systemic metabolic alterations, such as altered were corrected for age. Another important pendent of obesity. In subjects with FLD, lipid profile, insulin resistance, general result found by Tsuneto et al. was that BMI hepatic overproduction of glucose, very- or preferential abdominal obesity and/or and serum triglyceride levels increased low-density lipoproteins (VLDLs), C-reactive diabetes.1,2 steadily during the mean 12-year study period protein (CRP) and coagulation factors The real prevalence of FLD is not known, in subjects who developed FLD,4 whereas, increase the risk of type 2 diabetes and but the perception is that its prevalence is in the other group, BMI and triglyceride cardiovascular disease.1,6,10 Hyperglycemia increasing.3 In the general population, it is concentrations remained constant. This find- induces a series of alterations, including estimated that 20–45% of people have liver ing is in agreement with previous results endothelial dysfunction, cellular proliferation, steatosis. The prevalence increases to 57% in showing a strong positive correlation between changes in extracellular matrix conformation obese subjects, 70% in diabetic subjects and BMI and visceral and intrahepatic fat and impairment of LDL receptor-mediated 90% in morbidly obese people. The data on accumulation in subjects with FLD.2,6 More- uptake, decreasing the in vivo clearance the incidence of FLD are still scarce.3 In this over, hyperglycemia is a risk condition for of LDL. Small dense LDLs associated with context, the paper by Tsuneto et al.4 pub- FLD, independent of obesity: patients with high circulating VLDLs have a higher affinity lished in this issue of Hypertension Research is diabetes have a greater accumulation of intra- for intimal proteoglycans, leading to the very important. The authors evaluated the hepatic and visceral fat despite similar penetration of more LDL particles into the incidence of FLD in 1635 Nagasaki atomic BMIs.2,6 arterial wall. CRP can also accelerate athero- bomb survivors who were followed for a FLD is often considered to be the hepatic sclerosis by increasing the expression of plas- mean of 12 years: they showed an incidence component of metabolic syndrome.7 Meta- minogen activator inhibitor-1 and adhesion of 19.9 per 1000 people per year. Despite the bolic syndrome is a cluster of metabolic and molecules in endothelial cells, inhibiting limitation of the study cohort, namely, the cardiovascular risk factors that predicts dia- nitric oxide formation and increasing LDL subjects are all atomic bomb survivors and betes and cardiovascular disease (CVD) better uptake into macrophages.1,6,10 All these meta- thus the results cannot be translated to the than do any of its individual components.8 bolic abnormalities have been shown to general population, the data are quite similar The latest joint statement of the International directly or indirectly promote atherosclerosis; to those published by Bedogni et al.5 for the Diabetes Federation and the American Heart in fact, carotid intima-media thickness has Italian population examined in the Dionysos Association/National Heart, Lung, and Blood been found to be increased in subjects with study, which reported an incidence of 18.5 Institute qualifies a person as having meta- FLD.10,11 per 1000 people per year. bolic syndrome if he or she has at least three Despite all the evidence, FLD or increased abnormal findings from among the following: hepatic enzymes are not considered among abdominal obesity as defined by an increased the criteria indicating metabolic syndrome.8 waist circumference (population and country The paper by Tsuneto et al.clearlyshowsthat Dr A Gastaldelli is at the Consiglio Nazionale delle specific), low high-density lipoprotein (HDL) subjects who developed FLD had high blood Ricerche (CNR) of Clinical Physiology, Via Moruzzi 1, Pisa 56126, Italy. cholesterol, elevated blood pressure, elevated pressure, low HDL cholesterol, and a constant E-mail: [email protected] fasting glucose or elevated triglyceride con- increase in triglyceride concentrations and Commentary 547

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