کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9115710 1157149 2005 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Intestinal assembly and secretion of highly dense/lipid-poor apolipoprotein B48-containing lipoprotein particles in the fasting state: Evidence for induction by insulin resistance and exogenous fatty acids
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی علوم غدد
پیش نمایش صفحه اول مقاله
Intestinal assembly and secretion of highly dense/lipid-poor apolipoprotein B48-containing lipoprotein particles in the fasting state: Evidence for induction by insulin resistance and exogenous fatty acids
چکیده انگلیسی
Emerging evidence suggests that overproduction of intestinally derived apolipoprotein (apo) B48-containing lipoprotein particles may be an important contributor to both fasting and postprandial dyslipidemia in insulin-resistant states. Mechanisms regulating the assembly and secretion of apoB48-containing lipoproteins are not fully understood particularly in the diabetic/insulin-resistant intestine. In the present study, we have investigated the density profile of apoB48 lipoproteins assembled in primary hamster enterocytes. Both intracellular and secreted apoB48 particles were examined in intestinal enterocytes isolated from normal or insulin-resistant fructose-fed hamsters, as well as in enterocytes treated with exogenous oleic acid. Microsomal luminal contents and culture media were analyzed by discontinuous and sequential ultracentrifugation on sucrose and KBr gradients, respectively. ApoB48 was mostly secreted on VLDL-, LDL-, and denser HDL-sized particles in the fasting state. In pulse-chase labeling experiments, nascent apoB48-containing particles initially accumulated in the microsomal lumen as HDL-sized particles, with subsequent formation of apoB48-VLDL particles, with only a minute amount of chylomicrons observed. Treatment with 720 μmol/L of oleic acid, increased microsomal apoB48 HDL synthesis, and induced a marked shift toward lighter more buoyant particles. A marked enhancement in assembly of apoB48-containing lipoproteins was also observed in the microsomal lumen of fructose-fed hamster enterocytes, suggesting facilitated assembly and secretion of dense intestinal lipoprotein particles in insulin-resistant states. Overall, these observations suggest that a major proportion of apoB48-containing lipoprotein particles is assembled and secreted as highly dense, HDL-sized particles. The production of these small, dense, and potentially atherogenic apoB48 particles can be stimulated by increased free fatty acid flux as well as in insulin-resistant diabetes.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Metabolism - Volume 54, Issue 5, May 2005, Pages 689-697
نویسندگان
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