| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
Papers In Press, published online ahead of print December 1, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Atherosclerosis, Nutrition and Lipid Research, Washington University School of Medicine, St. Louis, MO 63110
Corresponding Author: gschonfe{at}im.wustl.edu
An unknown proportion of subjects with familial hypobetalipoproteinemia [FHBL] develops fatty liver. The fat content of livers was assessed in 21 representative FHBL subjects with truncations of apoB ranging from apoB-4 to apoB-89, and 14 matched controls by magnetic resonance spectroscopy [MRS]. Respective liver fat% were 16.7+/-11.5 and 3.3+/-2.9 [mean+/-SD] (p=0.001). In FHBL subjects, liver fat% was positively correlated with body mass index, and waist circumference, and areas under the insulin curves of 2h glucose tolerance tests. A similar pattern of correlations was present in controls. However, mean values for these variables were similar in FHBL and controls. This suggests that the degree of abdominal obesity may affect the severity of liver fat accumulation, but for any given degree of obesity FHBL subjects have more hepatic fat, probably due to reduced production of VLDL particles. VLDL-triglyceride [TG]-fatty acids arise from plasma and non-plasma sources such as lipids in the liver and other splanchnic tissues. To assess the relative contributions of each, [2H2]-palmitate was infused over 12h in 13 FHBL and 11 controls and the isotopic enrichment of plasma free palmitate and VLDL-TG-palmitate was determined by mass spectrometry, and the fraction of VLDL-TG originating from plasma and non-plasma sources was assessed using a compartmental model. Non-plasma sources contributed 51+/-15% in FHBL subjects versus 37+/-13% in controls (p=0.02). The correlation between liver fat % measured by MRS and the contribution from non-plasma sources was r=0.89 (p=0.0001) for FHBL subjects and r=0.69 (p=0.01) for controls, indicating that hepatic stores comprise a major component of the non-plasma lipid assembled into VLDL-TG. Thus, apoB truncation-producing mutations result in fatty liver and in altered assembly of VLDL-TG.
Revised on November 14, 2002
Accepted on November 22, 2002
Fatty liver in familial hypobetalipoproteinemia: triglyceride assembly into VLDL particles is affected by the extent of hepatic steatosis
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  A. van der Graaf, S. W. Fouchier, M. N. Vissers, J. C. Defesche, A. Wiegman, R. R. Sankatsing, B. A. Hutten, M. D. Trip, and J. J.P. Kastelein Familial Defective Apolipoprotein B and Familial Hypobetalipoproteinemia in One Family: Two Neutralizing Mutations Ann Intern Med, May 6, 2008; 148(9): 712 - 714. [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Hooper, K. Robertson, P. H. R. Barrett, K. G. Parhofer, F. M. van Bockxmeer, and J. R. Burnett Postprandial Lipoprotein Metabolism in Familial Hypobetalipoproteinemia J. Clin. Endocrinol. Metab., April 1, 2007; 92(4): 1474 - 1478. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. N. Reeds, W. T. Cade, B. W. Patterson, W. G. Powderly, S. Klein, and K. E. Yarasheski Whole-Body Proteolysis Rate Is Elevated in HIV-Associated Insulin Resistance. Diabetes, October 1, 2006; 55(10): 2849 - 2855. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Lin, Z. Chen, P. Yue, M. R. Averna, R. E. Ostlund Jr., M. A. Watson, and G. Schonfeld A targeted apoB38.9 mutation in mice is associated with reduced hepatic cholesterol synthesis and enhanced lipid peroxidation Am J Physiol Gastrointest Liver Physiol, June 1, 2006; 290(6): G1170 - G1176. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. Sankatsing, S. W. Fouchier, S. de Haan, B. A. Hutten, E. de Groot, J. J.P. Kastelein, and E. S.G. Stroes Hepatic and Cardiovascular Consequences of Familial Hypobetalipoproteinemia Arterioscler. Thromb. Vasc. Biol., September 1, 2005; 25(9): 1979 - 1984. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Lin, P. Yue, Y. Xie, N. O. Davidson, N. Sakata, R. E. Ostlund Jr., Z. Chen, and G. Schonfeld Reduced intestinal fat absorptive capacity but enhanced susceptibility to diet-induced fatty liver in mice heterozygous for ApoB38.9 truncation Am J Physiol Gastrointest Liver Physiol, July 1, 2005; 289(1): G146 - G152. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Lin, P. Yue, Z. Chen, and G. Schonfeld Hepatic triglyceride contents are genetically determined in mice: results of a strain survey Am J Physiol Gastrointest Liver Physiol, June 1, 2005; 288(6): G1179 - G1189. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Crooke, M. J. Graham, K. M. Lemonidis, C. P. Whipple, S. Koo, and R. J. Perera An apolipoprotein B antisense oligonucleotide lowers LDL cholesterol in hyperlipidemic mice without causing hepatic steatosis J. Lipid Res., May 1, 2005; 46(5): 872 - 884. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E L Thomas, G Hamilton, N Patel, R O'Dwyer, C J Dore, R D Goldin, J D Bell, and S D Taylor-Robinson Hepatic triglyceride content and its relation to body adiposity: a magnetic resonance imaging and proton magnetic resonance spectroscopy study Gut, January 1, 2005; 54(1): 122 - 127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Whitfield, P. H. R. Barrett, K. Robertson, M. F. Havlat, F. M. van Bockxmeer, and J. R. Burnett Liver Dysfunction and Steatosis in Familial Hypobetalipoproteinemia Clin. Chem., January 1, 2005; 51(1): 266 - 269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Garbow, X. Lin, N. Sakata, Z. Chen, D. Koh, and G. Schonfeld In vivo MRS measurement of liver lipid levels in mice J. Lipid Res., July 1, 2004; 45(7): 1364 - 1371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. J. van Greevenbroek, V. M. M-J. Vermeulen, and T. W. A. de Bruin Identification of novel molecular candidates for fatty liver in the hyperlipidemic mouse model, HcB19 J. Lipid Res., June 1, 2004; 45(6): 1148 - 1154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Tanoli, P. Yue, D. Yablonskiy, and G. Schonfeld Fatty liver in familial hypobetalipoproteinemia: roles of the APOB defects, intra-abdominal adipose tissue, and insulin sensitivity J. Lipid Res., May 1, 2004; 45(5): 941 - 947. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Chen, R. L. Fitzgerald, G. Li, N. O. Davidson, and G. Schonfeld Hepatic secretion of apoB-100 is impaired in hypobetalipoproteinemic mice with an apoB-38.9-specifying allele J. Lipid Res., January 1, 2004; 45(1): 155 - 163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Schonfeld Familial hypobetalipoproteinemia: a review J. Lipid Res., May 1, 2003; 44(5): 878 - 883. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Journal of Biological Chemistry |
| Molecular and Cellular Proteomics | ASBMB Today |
