Increased mediastinal fat and impaired left ventricular energy metabolism in young men with newly found fatty liver

Abstract

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 ‫؍‬ 21) or without (n ‫؍‬ 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. 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-

Epicardial fat, cardiac geometry and cardiac function in patients with non-alcoholic fatty liver disease: Association with the severity of liver disease

“…In the last years growing evidence also suggests that the increase in epicardial fat can be considered a cardiometabolic risk factor [32], being associated with the metabolic syndrome [33], with a diagnosis of NAFLD both by US or MR spectroscopy [14][15][16][17][18], with carotid atherosclerosis [34] and coronary artery disease [35]. Accordingly, we confirmed the association of epicardial fat thickness with older age, visceral obesity, hypertension and statin use, well-known factors associated with an increased cardiovascular risk.…”

“…The complex interplay between liver fat and heart function has been further demonstrated by studies reporting an association between NAFLD and epicardial fat thickness. Epicardial fat thickness, assessed by either magnetic resonance imaging (MRI) [14] or echocardiography [15,16] was higher in NAFLD subjects compared to non-NAFLD, and a correlation was reported between epicardial fat thickness and ALT levels [17], the severity of ultrasonographic (US) [15] or MR spectroscopy [18] steatosis, and the Nonalcoholic Activity Score (NAS) in un-adjusted analyses [16].…”

Increased risk of cardiovascular disease in non-alcoholic fatty liver disease: causal effect or epiphenomenon?

“…The main cross-sectional [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] and prospective [11,[32][33][34][35][36][37][38][39][40][41][42][43] studies on the association between NAFLD and intermediate markers of CVDor clinical outcomes are shown in Tables 1 and 2 of the Electronic supplementary material. NAFLD, endothelial dysfunction, early carotid atherosclerosis and left ventricular dysfunction NAFLD is associated with circulatory endothelial dysfunction [16,17], a marker of early atherosclerosis. Compared with non-steatotic controls, non-diabetic patients with NAFLD show a significant decrease in brachial artery flow-mediated vasodilation, which is related to the severity of NAFLD histology, independently of age, sex, BMI and HOMA-IR [16].…”

“…Similarly, patients with NAFLD, also in the absence of obesity, hypertension and diabetes, exhibit echocardiographic features of early left ventricular dysfunction [18] and impaired energy metabolism as measured by cardiac 31 P magnetic resonance spectroscopy [19].…”

Silibinin improves hepatic and myocardial injury in mice with nonalcoholic steatohepatitis

“…Myocardial fat causes alterations in substrate utilization (cardiac work/myocardial oxygen consumption) that occur early in the cascade of events leading to impaired ventricular contractility [9,10]. Recently, echocardiographic features of early left ventricular dysfunction and impaired energetics, measured by cardiac 31 Pmagnetic resonance spectroscopy, have been reported in NAFLD patients in the absence of obesity, hypertension and diabetes [11].…”