Visceral fat: A key mediator of steatohepatitis in metabolic liver disease

Abstract

Visceral obesity is intimately associated with metabolic disease and adverse health outcomes. However, a direct association between increasing amounts of visceral fat and end-organ inflammation and scarring has not been demonstrated. We examined the association between visceral fat and liver inflammation in patients with nonalcoholic fatty liver disease (NAFLD) to delineate the importance of visceral fat to progressive steatohepatitis and hence the inflammatory pathogenesis of the metabolic syndrome. We undertook a cross-sectional, proof of concept study in 38 consecutive adults with NAFLD at a tertiary liver clinic. All subjects had a complete physical examination, anthropometric assessment, and fasting blood tests on the day of liver biopsy. Abdominal fat volumes were assessed by magnetic resonance imaging within 2 weeks of liver biopsy. The extent of hepatic inflammation and fibrosis augmented incrementally with increases in visceral fat (P < 0.01). For each 1% increase in visceral fat, the odds ratio for increasing liver inflammation and fibrosis was 2.4 (confidence interval [CI]: 1.3-4.2) and 3.5 (CI: 1.7-7.1), respectively. Visceral fat remained an independent predictor of advanced steatohepatitis (odds ratio [OR] 2.1, CI: 1.1-4.2, P ‫؍‬ 0.05) and fibrosis (OR 2.9, CI: 1.4-6.3, P ‫؍‬ 0.006) even when controlled for insulin resistance and hepatic steatosis. Interleukin-6 (IL-6) levels, which correlated with visceral fat, also independently predicted increasing liver inflammation. Visceral fat was associated with all components of the metabolic syndrome. Conclusion: Visceral fat is directly associated with liver inflammation and fibrosis independent of insulin resistance and hepatic steatosis. Visceral fat should therefore be a central target for future interventions in nonalcoholic steatohepatitis and indeed all metabolic disease. (HEPATOLOGY 2008;48:449-457.)

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

“…Different lines of clinical studies showed that visceral fat [30], as well as other ectopic fat depots like the dorso-cervical fat [31], have a key role in the pathogenesis of NAFLD and especially in its histological severity. 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].…”

1296 Visceral Adipose Tissue Area as an Independent Risk Factor of Elevated Liver Enzyme in Nonalcoholic Fatty Liver Disease

“…32 Furthermore, visceral fat was directly associated with hepatic inflammation and fibrosis in a dose-dependent manner, independent of insulin resistance. 15 A strength of our study is the relatively large sample size, which allowed for a high-powered analysis of associations. Moreover, the subjects in this study are representative of the healthy population due to the characteristics of a health checkup.…”

Oxidative stress: New insights on the association of non-alcoholic fatty liver disease and atherosclerosis

“…Many evidences suggest that the distribution of body fat plays a more important role in obesity-associated comorbidities than the total body fat mass. Visceral adipose tissue (VAT) compared with subcutaneous fat (SCF) is a better predictor of hepatic steatosis and is associated with histological severity in NAFLD independent of IR and hepatic steatosis [42] . VAT is more lipolitically active on a per unit weight basis and exhibits greater IR than SCF [43][44][45] , causing enhanced peripheral lipolysis resulting in surplus-free fatty acid turn over into the liver [46] .…”