Fatty liver is characterized by metabolic abnormalities at the liver, but also at skeletal muscle and adipose tissue sites. It is hypothesized that the heart may be suffering metabolic alterations, and this study was undertaken to ascertain whether individuals with fatty liver have left ventricular (LV) alterations of energy metabolism, structure, and function and abnormal amounts of epicardial fat as a specific marker of visceral fat accumulation. To this end we studied young, nondiabetic men matched for anthropometric features with (n โซุโฌ 21) or without (n โซุโฌ 21) fatty liver by means of (1) cardiac magnetic resonance imaging (MRI); (2) cardiac 31 P-MR spectroscopy (MRS); and (3) hepatic 1 H-MRS to assess quantitatively the intrahepatic fat (IHF) content. Insulin sensitivity was determined by the updated HOMA-2 computer model. Individuals with fatty liver showed reduced insulin sensitivity, increased serum free fatty acid (FFA), and Eselectin, abnormal adipokine concentrations, and higher blood pressure. LV morphology and systolic and diastolic functions were not different; however, in the scanned intrathoracic region, the intrapericardial (7.8 ุ 3.1 versus 5.9 ุ 2.5 cm 2 ; P < 0.05) and extrapericardial (11.7 ุ 6.1 versus 7.8 ุ 3.2 cm 2 ; P < 0.03) fat was increased in men with fatty liver compared with those without fatty liver. 1 The phosphocreatine (PCr)/adenosine triphosphate (ATP) ratio, a recognized in vivo marker of myocardial energy metabolism, was reduced in men with fatty liver in comparison with normals (1.85 ุ 0.35 versus 2.11 ุ 0.31; P < 0.016). In conclusion, in newly found individuals with fatty liver, fat was accumulated in the epicardial area and despite normal LV morphological features and systolic and diastolic functions, they had abnormal LV energy metabolism. (HEPATOLOGY 2008;47:51-58.) See Editorial on Page 1 N onalcoholic fatty liver (NAFL) is a feature of the insulin resistance syndrome 1,2 and a typical aspect of body composition related to visceral adiposity. 3 Multiple metabolic abnormalities in organs and tissues under the influence of insulin were reported: impaired insulin-mediated inhibition of hepatic glucose production was reported at the liver site, 1,4 impaired insulin-stimulated glucose metabolism was shown at the level of the skeletal muscle, 1,5,6 and impaired insulin-dependent control on lipolysis was detected at the level of the adipose tissue. 1,4 The heart is another organ whose metabolism may be influenced by insulin resistance. Few insights are available about cardiac metabolism in patients with NAFL because of the difficulties of studying nonin-