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Journal of Lipid Research, Vol. 44, 470-478, March 2003
Copyright © 2003 by Lipid Research, Inc.

Fatty liver in familial hypobetalipoproteinemia

Gustav Schonfeld^1,*, Bruce W. Patterson^*, Dmitriy A. Yablonskiy, Tariq S. K. Tanoli, Maurizio Averna^**, Nizar Elias, Pin Yue^* and Joseph Ackerman^*,,

^* Departments of Internal Medicine, Washington University, St. Louis, MO
Radiology, Washington University, St. Louis, MO
Chemistry, Washington University, St. Louis, MO
^** Department of Medicine, University of Palermo, Italy
Department of Internal Medicine-A, B'nai-Zion Medical Center, Haifa, Israel

¹ To whom correspondence should be addressed. e-mail: gschonfe{at}im.wustl.edu

Familial hypobetalipoproteinemia (FHBL) subjects may develop fatty liver. Liver fat was assessed in 21 FHBL with six different apolipoprotein B (apoB) truncations (apoB-4 to apoB-89) and 14 controls by magnetic resonance spectroscopy (MRS). Liver fat percentages were 16.7 ± 11.5 and 3.3 ± 2.9 (mean ± SD) (P = 0.001). Liver fat percentage was positively correlated with body mass index, waist circumference, and areas under the insulin curves of 2 h glucose tolerance tests, suggesting that obesity may affect the severity of liver fat accumulation in both groups. Despite 5-fold differences in liver fat percentage, mean values for obesity and insulin indexes were similar. Thus, for similar degrees of obesity, FHBL subjects have more hepatic fat. VLDL-triglyceride (TG)-fatty acids arise from plasma and nonplasma sources (liver and splanchnic tissues). To assess the relative contributions of each, [²H₂]palmitate was infused over 12 h in 13 FHBL subjects and 11 controls. Isotopic enrichment of plasma free palmitate and VLDL-TG-palmitate was determined by mass spectrometry. Non-plasma sources contributed 51 ± 15% in FHBL and 37 ± 13% in controls (P = 0.02). Correlations of liver fat percentage and percent VLDL-TG-palmitate from liver were r = 0.89 (P = 0.0001) for FHBL subjects and r = 0.69 (P = 0.01) for controls.

Thus, apoB truncation-producing mutations result in fatty liver and in altered assembly of VLDL-TG.

Abbreviations: ER, endoplasmic reticulum; FA, fatty acids; FHBL, familial hypobetalipoproteinemia; MRS, magnetic resonance spectroscopy; NAFL, nonalcoholic fatty liver; NEFA, nonesterified fatty acids; PR, production rate; TG, triglyceride; TTR, tracer/tracee ratio; Ra, rate of appearance

Supplementary key words nonalcoholic fatty liver • nonesterified fatty acids • very low density lipoprotein assembly • magnetic resonence spectroscopy

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