Fatty liver in familial hypobetalipoproteinemia: triglyceride assembly into VLDL particles is affected by the extent of hepatic steatosis.
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.
Schonfeld
Gustav
G
Department of Internal Medicine, Washington University, St. Louis, MO, USA. gschonfe@im.wustl.edu
Patterson
Bruce W
BW
Yablonskiy
Dmitriy A
DA
Tanoli
Tariq S K
TS
Averna
Maurizio
M
Elias
Nizar
N
Yue
Pin
P
Ackerman
Joseph
J
D000328:Adult; D015992:Body Mass Index; D004041:Dietary Fats; D005234:Fatty Liver / Q000150:complications* / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D006995:Hypobetalipoproteinemias / Q000097:blood / Q000150:complications* / Q000235:genetics / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008107:Liver Diseases / Q000097:blood / Q000150:complications* / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000378:metabolism; D010169:Palmitic Acids / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D012720:Severity of Illness Index; D014280:Triglycerides / Q000378:metabolism*
D004041:Dietary Fats; D008079:Lipoproteins, VLDL; D010169:Palmitic Acids; D014280:Triglycerides