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Intrahepatic Fat Accumulation and Alterations in Lipoprotein Composition in Obese Adolescents

A perfect proatherogenic state

¹ Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut
² Department of Health, State University of Feira de Santana, Feira De Santana, Brazil
³ Department of Internal Medicine and the Howard Hughes Institute, Yale University School of Medicine, New Haven, Connecticut
⁴ LipoScience, Raleigh, North Carolina

Address correspondence and reprint requests to Sonia Caprio, MD, Yale University School of Medicine, Department of Pediatrics, 330 Cedar St., P.O. Box 208064, New Haven, CT 06520. E-mail: sonia.caprio{at}yale.edu

OBJECTIVE—Among other metabolic consequences, a dyslipidemic profile often accompanies childhood obesity. In adults, type 2 diabetes 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.

RESEARCH DESIGN AND METHODS—Using fast magnetic resonance imaging, we measured intrahepatic fat content in 49 obese adolescents with normal glucose tolerance. 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 nuclear magnetic resonance spectroscopy.

RESULTS—Overall, the high-HFF group had 88% higher concentrations of large VLDL compared with 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 proatherogenic phenotype was strongly related to the intrahepatic lipid content.

Abbreviations: EMCL, extramyocellular triglyceride content • HFF, hepatic fat fraction • IMCL, intramyocellular triglyceride content • MRI, magnetic resonance imaging • NMR, nuclear magnetic resonance • WBISI, whole-body insulin sensitivity index

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