Intestinal lipoprotein assembly

ArticleinCurrent Opinion in Lipidology 16(3):281-5 · July 2005with8 Reads
DOI: 10.1097/01.mol.0000169347.53568.5a · Source: PubMed
  • 44.4 · State University of New York Downstate Medical Center
  • 20.39 · King Saud University
  • 30.41 · State University of New York Downstate Medical Center
  • 36.26 · State University of New York Downstate Medical Center
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.
    • "Chylomicron retention disease (CMRD) or Anderson's Disease (OMIM #607689) is a rare, autosomic recessive disorder usually diagnosed in infants presenting with chronic diarrhea, failure to thrive, hypocholesterolemia and low fat-soluble vitamin levels (Anderson et al., 1961; Lee and Hegele, 2014; Cefalù et al., 2015). The specific molecular defect was identified in 2003 and consists of mutations in the SAR1B gene which encodes for intracellular Sar1b protein (Strich et al., 1993; Shoulders et al., 2004; Hussain et al., 2005; Cefalù et al., 2010). This protein is involved in the transport of chylomicron through the secretory pathway (see Section Chylomicron Secretion). "
    [Show abstract] [Hide abstract] ABSTRACT: Intestinal lipoprotein production is a multistep process, essential for the absorption of dietary fats and fat-soluble vitamins. Chylomicron assembly begins in the endoplasmic reticulum with the formation of primordial, phospholipids-rich particles that are then transported to the Golgi for secretion. Several classes of transporters play a role in the selective uptake and/or export of lipids through the villus enterocytes. Once secreted in the lymph stream, triglyceride-rich lipoproteins (TRLs) are metabolized by Lipoprotein lipase (LPL), which catalyzes the hydrolysis of triacylglycerols of very low density lipoproteins (VLDLs) and chylomicrons, thereby delivering free fatty acids to various tissues. Genetic mutations in the genes codifying for these proteins are responsible of different inherited disorders affecting chylomicron metabolism. This review focuses on the molecular pathways that modulate the uptake and the transport of lipoproteins of intestinal origin and it will highlight recent findings on TRLs assembly.
    Full-text · Article · Mar 2015
    • "The circulating plasma TGs are formed mainly from two major sources: intestinally derived chylomicrons (CMs) and hepatically derived very low density lipoproteins (VLDL) [22]. In the intestinal cells, dietary TGs together with dietary cholesterol are packed and, after binding to apolipoprotein (apo) B-48 (mediated by microsomal triglyceride transport protein, MTP), the CMs are formed, which are then transported via lymphatic vesselsblood circulation to other cells of the body [23, 24]. In the hepatic cells the newly synthetized TGs are binding to apo B-100, also mediated by MTP, and formed VLDL particles which are released to blood circulation. "
    [Show abstract] [Hide abstract] ABSTRACT: Hypertriglyceridemia (HTG) is a feature of numerous metabolic disorders including dyslipidemias, metabolic syndrome, and diabetes mellitus type 2 and can increase the risk of premature coronary artery disease. HTG may also be due to genetic factors (called primary HTG) and particularly the severe/extreme HTG (SEHTG), which is a usually rare genetic disorder. Even rarer are secondary cases of SEHTG caused by autoimmune disease. This review considers the causes of SEHTG, and their management including treatment with low density lipoprotein apheresis and analyzes the original findings.
    Full-text · Article · Dec 2014
    • "In the postprandial period, it is assumed that the major fraction of vitamin A and carotenoids are incorporated into chylomicrons that are secreted into the lymph [115,116], vitamin A being recovered as retinyl esters, while carotenoids are recovered in their free forms [90,117]. It was shown in Caco-2 cells that only newly-synthesized retinyl esters could be incorporated into chylomicrons [47], which suggests that retinyl ester synthesis is coupled to chylomicron assembly. "
    [Show abstract] [Hide abstract] ABSTRACT: Vitamin A deficiency is a public health problem in most developing countries, especially in children and pregnant women. It is thus a priority in health policy to improve preformed vitamin A and/or provitamin A carotenoid status in these individuals. A more accurate understanding of the molecular mechanisms of intestinal vitamin A absorption is a key step in this direction. It was long thought that β-carotene (the main provitamin A carotenoid in human diet), and thus all carotenoids, were absorbed by a passive diffusion process, and that preformed vitamin A (retinol) absorption occurred via an unidentified energy-dependent transporter. The discovery of proteins able to facilitate carotenoid uptake and secretion by the enterocyte during the past decade has challenged established assumptions, and the elucidation of the mechanisms of retinol intestinal absorption is in progress. After an overview of vitamin A and carotenoid fate during gastro-duodenal digestion, our focus will be directed to the putative or identified proteins participating in the intestinal membrane and cellular transport of vitamin A and carotenoids across the enterocyte (i.e., Scavenger Receptors or Cellular Retinol Binding Proteins, among others). Further progress in the identification of the proteins involved in intestinal transport of vitamin A and carotenoids across the enterocyte is of major importance for optimizing their bioavailability.
    Full-text · Article · Sep 2013
Show more