TY - JOUR
T1 - Fatty liver in familial hypobetalipoproteinemia
T2 - Triglyceride assembly into VLDL particles is affected by the extent of hepatic steatosis
AU - Schonfeld, Gustav
AU - Patterson, Bruce W.
AU - Yablonskiy, Dmitriy A.
AU - Tanoli, Tariq S.K.
AU - Averna, Maurizio
AU - Elias, Nizar
AU - Yue, Pin
AU - Ackerman, Joseph
PY - 2003/3
Y1 - 2003/3
N2 - 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. Nonplasma 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.
AB - 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. Nonplasma 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.
KW - Magnetic resonence spectroscopy
KW - Nonalcoholic fatty liver
KW - Nonesterified fatty acids
KW - Very low density lipoprotein assembly
UR - http://www.scopus.com/inward/record.url?scp=0038620476&partnerID=8YFLogxK
U2 - 10.1194/jlr.M200342-JLR200
DO - 10.1194/jlr.M200342-JLR200
M3 - Article
C2 - 12562873
AN - SCOPUS:0038620476
VL - 44
SP - 470
EP - 478
JO - Journal of Lipid Research
JF - Journal of Lipid Research
SN - 0022-2275
IS - 3
ER -