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Intrahepatic Fat Accumulation and Alterations in Lipoprotein Composition in Obese Adolescents: A Perfect Pro-Atherogenic State

¹Department of Pediatrics, Yale University School of Medicine, New Haven, CT;
²State University of Feira de Santana, Feira De Santana, Brazil;
³Internal Medicine and the Howard Hughes Institute, Yale University School of Medicine, New Haven, CT;
⁴Liposcience Inc., Raleigh, NC

sonia.caprio{at}yale.edu

ABSTRACT

Background: Among other metabolic consequences, a dyslipidemic profile often accompanies childhood obesity. In adults, Type 2 Diabetes (T2DM) and hepatic steatosis have been shown to alter lipoprotein subclass distribution and size; however, these alterations have not yet been shown in children or adolescents. Therefore, our objective was to determine the effect of hepatic steatosis on lipoprotein concentration and size in obese adolescents.

Methods and Results: Using fast-MRI, we measured intrahepatic fat content in 49 obese normal glucose tolerant adolescents. The presence or absence of hepatic steatosis was determined by a threshold value for hepatic fat fraction (HFF) of 5.5%; therefore, the cohort was divided into two groups (HFF > or < 5.5%). Fasting lipoprotein subclasses were determined using NMR spectroscopy. Overall, the high HFF group had 88% higher concentrations of large VLDL compared to the low HFF group (p<0.001). Likewise, the high HFF group had significantly higher concentrations of small dense LDL (p<0.007); however, the low HFF group had significantly higher concentrations of large HDL (p<0.001). Stepwise multiple regression analysis revealed that high HFF was the strongest single correlate, accounting for 32.6% of the variance in large VLDL concentrations (p<0.002).

Conclusions: The presence of fatty liver was associated with a pronounced dyslipidemic profile characterized by large VLDL, small dense LDL and decreased large HDL concentrations. This pro-atherogenic phenotype was strongly related to the intrahepatic lipid content.

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