Circulating triglyceride levels are dictated not only by dietary intake but also by hepatic triglyceride production, which is elevated in NAFLD. This suggests that NAFLD may be exerting its negative effects on vascular function indirectly via increasing blood triglyceride levels. As a result, we hypothesized that the elevated liver fat levels in obesity would be linked to aortic stiffness, and that effect would, at least in part, be mediated indirectly via increasing serum triglyceride levels. Should © 2015 American Heart Association, Inc. Objective-To investigate the relationship between hepatic fat content, circulating triglyceride levels and aortic stiffness in adult and childhood obesity. Approach and Results-Seventy-seven adults and 18 children across a wide range of body mass index (18.5-52.6 kg/ m 2; percentile 8-100) with no identifiable cardiac risk factors underwent; 1H-magnetic resonance spectroscopy to quantify hepatic fat content and magnetic resonance imaging to assess aortic pulse wave velocity (PWV) and regional distensibility. In adults, multivariable regression showed age (β=0.09; P=0.02), liver fat (β=2.5; P=0.04), and serum triglyceride (β=0.47; P=0.01) to be independent predictors of PWV. Age and blood pressure-adjusted, moderated regression showed that 43% of the total negative effect of hepatic fat on PWV is attributable to indirect effects via increased triglyceride (P=0.005). In addition, regional distensibility was positively correlated with hepatic fat (ascending; r=−0.35; descending, r=−0.23; abdominal, r=−0.41; all P<0.001). Similar to that seen in adults, PWV (r=0.72; P<0.001) and abdominal regional distensibility (r=−0.52; P<0.001) were correlated with liver fat in children. Conclusions-Increasing age, liver fat, and triglyceride are all related to increased aortic stiffness in adults. Even when controlling for the effects of age and blood pressure, hepatic fat has a negative effect on PWV, with substantial indirect effect occurring via increased circulating triglyceride level. This relationship between hepatic fat and aortic stiffness occurs early in the obesity process and is also seen in children. As such, hepatic fat content is a potential therapeutic target to treat the elevated vascular risk in obesity. regional aortic distensibility (AD) 14 and abdominal visceral fat, 1H magnetic resonance spectroscopy assessment of liver fat content, dual-energy x-ray absorptiometry assessment of total fat mass, and fasting blood tests for serum triglyceride levels.
Materials and MethodsMaterials and Methods are available in the online-only Data Supplement.
ResultsA summary of the anthropometric data for the adult and childhood study groups is shown in Table 1. Table 3).
Adult Cohort
Hepatic Fat Content in AdultsStepwise multivariable regression of these variables revealed showed triglyceride (β=3.6; P=0.009) and liver fat (β=2.5; P=0.008) to be independent predictors of increased PWV in this model (overall R 2 of the model 0.42; P<0.001; Table 4). To further explore the relationship be...