title: Fatty liver in familial hypobetalipoproteinemia: triglyceride assembly into VLDL particles is affected by the extent of hepatic steatosis.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Washington University, St. Louis, MO, USA. gschonfe@im.wustl.edu
authors.forename: Gustav
authors.initials: G
authors.lastname: Schonfeld
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Patterson
authors.forename: Dmitriy A
authors.initials: DA
authors.lastname: Yablonskiy
authors.forename: Tariq S K
authors.initials: TS
authors.lastname: Tanoli
authors.forename: Maurizio
authors.initials: M
authors.lastname: Averna
authors.forename: Nizar
authors.initials: N
authors.lastname: Elias
authors.forename: Pin
authors.initials: P
authors.lastname: Yue
authors.forename: Joseph
authors.initials: J
authors.lastname: Ackerman
mesh_terms: 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*
chemical_list: D004041:Dietary Fats; D008079:Lipoproteins, VLDL; D010169:Palmitic Acids; D014280:Triglycerides