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
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.
Available from: Hannelore Daniel
- "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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ABSTRACT: Small intestine and liver greatly contribute to whole body lipid, cholesterol and phospholipid metabolism but to which extent cholesterol and phospholipid handling in these tissues is affected by high fat Western-style obesogenic diets remains to be determined.
We therefore measured cholesterol and phospholipid concentration in intestine and liver and quantified fecal neutral sterol and bile acid excretion in C57Bl/6 N mice fed for 12 weeks either a cholesterol-free high carbohydrate control diet or a high fat Western diet containing 0.03% (w/w) cholesterol. To identify the underlying mechanisms of dietary adaptations in intestine and liver, changes in gene expression were assessed by microarray and qPCR profiling, respectively.
Mice on Western diet showed increased plasma cholesterol levels, associated with the higher dietary cholesterol supply, yet, significantly reduced cholesterol levels were found in intestine and liver. Transcript profiling revealed evidence that expression of numerous genes involved in cholesterol synthesis and uptake via LDL, but also in phospholipid metabolism, underwent compensatory regulations in both tissues. Alterations in glycerophospholipid metabolism were confirmed at the metabolite level by phospolipid profiling via mass spectrometry.
Our findings suggest that intestine and liver react to a high dietary fat intake by an activation of de novo cholesterol synthesis and other cholesterol-saving mechanisms, as well as with major changes in phospholipid metabolism, to accommodate to the fat load.
BMC Genomics 03/2012; 13(1):84. DOI:10.1186/1471-2164-13-84 · 3.99 Impact Factor
Available from: Erik Eckhardt
- "IEC secrete a distinct class of large lipoprotein particles in the postprandial state, the chylomicrons , . These particles enable transport of intestinally absorbed, poorly soluble long-chain triglycerides (LCT) from the gut to other tissues. "
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ABSTRACT: A small fraction of dietary protein survives enzymatic degradation and is absorbed in potentially antigenic form. This can trigger inflammatory responses in patients with celiac disease or food allergies, but typically induces systemic immunological tolerance (oral tolerance). At present it is not clear how dietary antigens are absorbed. Most food staples, including those with common antigens such as peanuts, eggs, and milk, contain long-chain triglycerides (LCT), which stimulate mesenteric lymph flux and postprandial transport of chylomicrons through mesenteric lymph nodes (MLN) and blood. Most dietary antigens, like ovalbumin (OVA), are emulsifiers, predicting affinity for chylomicrons. We hypothesized that chylomicron formation promotes intestinal absorption and systemic dissemination of dietary antigens.
Absorption of OVA into MLN and blood was significantly enhanced when OVA was gavaged into fasted mice together with LCT compared with medium-chain triglycerides (MCT), which do not stimulate chylomicron formation. The effect of LCT was blocked by the addition of an inhibitor of chylomicron secretion, Pluronic L-81. Adoptively transferred OVA-specific DO11.10 T-cells proliferated more extensively in peripheral lymph nodes when OVA was gavaged with LCT than with MCT or LCT plus Pluronic L-81, suggesting that dietary OVA is systemically disseminated. Most dietary OVA in plasma was associated with chylomicrons, suggesting that these particles mediate systemic antigen dissemination. Intestinal-epithelial CaCo-2 cells secreted more cell-associated, exogenous OVA when stimulated with oleic-acid than with butyric acid, and the secreted OVA appeared to be associated with chylomicrons.
Postprandial chylomicron formation profoundly affects absorption and systemic dissemination of dietary antigens. The fat content of a meal may affect immune responses to dietary antigens by modulating antigen absorption and transport.
PLoS ONE 12/2009; 4(12):e8442. DOI:10.1371/journal.pone.0008442 · 3.23 Impact Factor
Available from: M Mahmood Hussain
- "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.
Cell metabolism 06/2008; 7(5):445-55. DOI:10.1016/j.cmet.2008.03.005 · 17.57 Impact Factor
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