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J. Lipid Res.
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A more recent version of this article appeared on May 1, 2004

Papers In Press, published online ahead of print February 16, 2004
J. Lipid Res., doi:10.1194/jlr.M300508-JLR200
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Submitted on December 11, 2003
Revised on January 14, 2004
Accepted on January 27, 2004

Fatty liver in familial hypobetalipoproteinemia: roles of the APOB defects, intra-abdominal adipose tissue, and insulin sensitivity

Tariq Tanoli, Pin Yue, Dmitriy Yablonskiy, and Gustav Schonfeld

Endocrinology, Diabetes & Lipid Research, Washington University School of Medicine, St Louis, MI 63110

Corresponding Author: gschonfe{at}im.wustl.edu

Fatty liver is frequent in the apoB-defective genetic form of familial hypobetalipoproteinemia [FHBL], but inter-individual variability in liver fat is large. To explain this, we assessed the roles of metabolic factors in 32 affected family members with apoB-defective FHBL, and 33 related and unrelated normo-lipidemic controls, matched for age, sex, and indexes of adiposity. Two-hour, 75 gm oral glucose tests, with measurements of plasma glucose and insulin levels, and body mass indexes, waist/hip ratios were obtained. Abdominal subcutaneous [SAT], intra-peritoneal [IPAT], and retro-peritoneal [RPAT] adipose masses were quantified by magnetic resonance [MR] imaging and hepatic fat by MR spectroscopy. Mean [±SD] liver fat% of FHBL and controls were 14.8±12.0 and 5.2±5.9, respectively [p=0.001]. Means for the above measures of obesity and insulin action were similar in the two groups. Important determinants of liver fat% were FHBL-affected status, IPAT, and AUC-insulin in both groups, but the strongest predictors were IPAT in FHBL [partial R2= 0.55, p<0.0002], and AUC-insulin in controls [partial R2=0.59, p=0.0001]. Regression of liver fat% on intra-peritoneal fat was significantly greater for FHBL than for controls [p<0.001]. In sum, because apoB-defective FHBL imparts heightened susceptibility to liver triglyceride accumulation, increasing IPAT and insulin resistance exert greater liver fat-raising effects in FHBL.


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