Intestinal lipoprotein assembly in apobec-1-/- mice reveals subtle alterations in triglyceride secretion coupled with a shift to larger lipoproteins

被引:32
作者
Xie, Y
Nassir, F
Luo, JY
Buhman, K
Davidson, NO
机构
[1] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Dept Mol Biol & Pharmacol, St Louis, MO 63110 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 2003年 / 285卷 / 04期
关键词
chylomicrons; very low-density lipoproteins; apolipoprotein B-100; apolipoprotein B-48;
D O I
10.1152/ajpgi.00202.2003
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Mammalian enterocytes express apolipoprotein (apo) B-48, which is produced after posttranscriptional RNA editing of the nuclear apoB-100 transcript by the catalytic deaminase apobec-1. Earlier studies in apobec-1 -/- mice revealed an apoB-100-only lipoprotein profile but no gross defects in triglyceride absorption. However, subtle defects may have been obscured by the mixed genetic background. In addition, the intrinsic susceptibility to proteolytic degradation of intestinal apoB-100 and apoB-48 has been questioned. Accordingly, we examined triglyceride absorption, intestinal apoB expression, and lipoprotein secretion in apobec-1 -/- mice backcrossed into a C57BL/6 background. Inbred apobec-1 -/- mice absorb triglyceride normally, yet secrete triglyceride-rich lipoproteins more slowly than wildtype congenic controls. There was comparable induction of apoB synthesis in response to fat feeding in both genotypes, but apoB-100 was preferentially retained and more extensively degraded than apoB-48. By contrast, synthesis, secretion, and content of apo A-IV were indistinguishable in apobec1-/- and wild-type mice with 100% recovery, suggesting no degradation of this apoprotein in either genotype. Newly secreted lipoproteins from isolated enterocytes of wild-type mice revealed apoB-48 in both high-density lipoproteins and very low-density lipoproteins. By contrast, apobec-1 -/- mice secreted apoB-100-containing particles that were almost exclusively in the low and very low-density lipoproteins range with no apoB-100-containing high-density lipoproteins. These studies establish the existence of preferential degradation of intestinal apoB-100 and subtle defects in triglyceride secretion in apobec-1 -/- mice, coupled with a shift to the production of larger particles, findings that suggest an important divergence in intestinal lipoprotein assembly pathways with the different isoforms of apoB.
引用
收藏
页码:G735 / G746
页数:12
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