Intestinal lipoprotein assembly. Curr Opin Lipidol

Department of Anatomy and Cell Biology, SUNY Downstate Medical Center, Brooklyn, New York, USA.
Current Opinion in Lipidology (Impact Factor: 5.66). 07/2005; 16(3):281-5. DOI: 10.1097/01.mol.0000169347.53568.5a
Source: PubMed


The assembly of intestinal lipoproteins is critical for the transport of fat and fat-soluble vitamins. In this review we propose a nomenclature for these lipoproteins and have summarized recent data about their intracellular assembly and factors that modulate their secretion.
The assembly and secretion of intestinal lipoproteins increases with the augmented synthesis of apoB, apoAIV and lipids. Chylomicron assembly begins with the formation of primordial, phospholipid-rich particles in the membrane, and their conversion to large chylomicrons occurs in the lumen of the smooth endoplasmic reticulum. Chylomicrons are transported from the endoplasmic reticulum via specialized vesicles to the Golgi for secretion. The identification of genetic mutations in chylomicron retention disease indicates that Sar1b may play a critical role in this process. In addition to chylomicron assembly, intestinal cells have been shown to transport dietary cholesterol via apoB-independent pathways, such as efflux.
Understanding the mechanisms involved in the intracellular transport of chylomicrons and chylomicron-independent secretion pathways are expected to be the next frontiers in the field of intestinal lipoprotein assembly and secretion.

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    • "Phospholipid scramblases represent a group of homologous ATP-independent bidirectional lipid translocators, involved in generation and maintenance of lipid asymmetry in the plasma membrane and are conserved in all eukaryotes [54,55]. Fat processing in intestinal cells causes, at least transiently, a rearrangement of plasma cell membranes, increases membrane synthesis and vesicular trafficking, with a need for a remodeling of all cellular membrane compartments [56,57]. Although the biological functions of the phospholipid scramblases 2 and 4 need to be determined, these changes may be taken as a signature of major alterations in PL metabolism in the intestinal epithelium, induced by Western diet feeding. "
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    BMC Genomics 03/2012; 13(1):84. DOI:10.1186/1471-2164-13-84 · 3.99 Impact Factor
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    • "IEC secrete a distinct class of large lipoprotein particles in the postprandial state, the chylomicrons [8], [9]. These particles enable transport of intestinally absorbed, poorly soluble long-chain triglycerides (LCT) from the gut to other tissues. "
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    PLoS ONE 12/2009; 4(12):e8442. DOI:10.1371/journal.pone.0008442 · 3.23 Impact Factor
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    • "Primary enterocytes from WT and KO mice (Iqbal et al., 2003; Iqbal and Hussain, 2005) were suspended in 4 ml of DMEM containing 1 μCi/ml of [ 3 H]cholesterol and incubated at 37°C. Enterocytes were incubated for 1 hr with micelles containing 1.2 mM oleic acid (Iqbal et al., 2003; Iqbal and Hussain, 2005). After 2 hr, enterocytes were centrifuged and supernatants were subjected to density gradient ultracentrifugation. "
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    ABSTRACT: Microsomal triglyceride transfer protein (MTP) is needed to assemble chylomicrons in the endoplasmic reticulum (ER) of enterocytes. We explored the role of an ER stress protein, inositol-requiring enzyme 1beta (IRE1beta), in regulating this process. High-cholesterol and high-fat diets decreased intestinal IRE1beta mRNA in wild-type mice. Ire1b(-/-) mice fed high-cholesterol and high-fat diets developed more pronounced hyperlipidemia because these mice secreted more chylomicrons and expressed more intestinal MTP, though not hepatic MTP, than wild-type mice did. Chylomicron secretion and MTP expression also were increased in primary enterocytes isolated from cholesterol-fed Ire1b(-/-) mice. There was no correlation between ER stress and MTP expression. Instead, cell culture studies revealed that IRE1beta, but not its ubiquitous homolog IRE1alpha, decreased MTP mRNA through increased posttranscriptional degradation. Conversely, knockdown of IRE1beta enhanced MTP expression. These studies show that IRE1beta plays a role in regulating MTP and in chylomicron production.
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