Insights from human congenital disorders of intestinal lipid metabolism
The intestine must challenge the profuse daily flux of dietary fat that serves as a vital source of energy and as an essential component of cell membranes. The fat absorption process takes place in a series of orderly and interrelated steps, including the uptake and translocation of lipolytic produc...
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doaj-6d33c669419d4f37826455fb25594a422021-04-28T05:57:17ZengElsevierJournal of Lipid Research0022-22752015-05-01565945962Insights from human congenital disorders of intestinal lipid metabolismEmile Levy0To whom correspondence should be addressed.; Research Centre, CHU Sainte-Justine and Department of Nutrition, Université de Montréal, Montreal, Quebec H3T 1C5, CanadaThe intestine must challenge the profuse daily flux of dietary fat that serves as a vital source of energy and as an essential component of cell membranes. The fat absorption process takes place in a series of orderly and interrelated steps, including the uptake and translocation of lipolytic products from the brush border membrane to the endoplasmic reticulum, lipid esterification, Apo synthesis, and ultimately the packaging of lipid and Apo components into chylomicrons (CMs). Deciphering inherited disorders of intracellular CM elaboration afforded new insight into the key functions of crucial intracellular proteins, such as Apo B, microsomal TG transfer protein, and Sar1b GTPase, the defects of which lead to hypobetalipoproteinemia, abetalipoproteinemia, and CM retention disease, respectively. These “experiments of nature” are characterized by fat malabsorption, steatorrhea, failure to thrive, low plasma levels of TGs and cholesterol, and deficiency of liposoluble vitamins and essential FAs. After summarizing and discussing the functions and regulation of these proteins for reader's comprehension, the current review focuses on their specific roles in malabsorptions and dyslipidemia-related intestinal fat hyperabsorption while dissecting the spectrum of clinical manifestations and managements. The influence of newly discovered proteins (proprotein convertase subtilisin/kexin type 9 and angiopoietin-like 3 protein) on fat absorption has also been provided. Finally, it is stressed how the overexpression or polymorphism status of the critical intracellular proteins promotes dyslipidemia and cardiometabolic disorders.http://www.sciencedirect.com/science/article/pii/S0022227520312359hypobetalipoproteinemiaabetalipoproteinemiachylomicron retention diseaseintestinal fat malabsorptionapolipoprotein B-48microsomal triglyceride transfer protein |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Emile Levy |
spellingShingle |
Emile Levy Insights from human congenital disorders of intestinal lipid metabolism Journal of Lipid Research hypobetalipoproteinemia abetalipoproteinemia chylomicron retention disease intestinal fat malabsorption apolipoprotein B-48 microsomal triglyceride transfer protein |
author_facet |
Emile Levy |
author_sort |
Emile Levy |
title |
Insights from human congenital disorders of intestinal lipid metabolism |
title_short |
Insights from human congenital disorders of intestinal lipid metabolism |
title_full |
Insights from human congenital disorders of intestinal lipid metabolism |
title_fullStr |
Insights from human congenital disorders of intestinal lipid metabolism |
title_full_unstemmed |
Insights from human congenital disorders of intestinal lipid metabolism |
title_sort |
insights from human congenital disorders of intestinal lipid metabolism |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2015-05-01 |
description |
The intestine must challenge the profuse daily flux of dietary fat that serves as a vital source of energy and as an essential component of cell membranes. The fat absorption process takes place in a series of orderly and interrelated steps, including the uptake and translocation of lipolytic products from the brush border membrane to the endoplasmic reticulum, lipid esterification, Apo synthesis, and ultimately the packaging of lipid and Apo components into chylomicrons (CMs). Deciphering inherited disorders of intracellular CM elaboration afforded new insight into the key functions of crucial intracellular proteins, such as Apo B, microsomal TG transfer protein, and Sar1b GTPase, the defects of which lead to hypobetalipoproteinemia, abetalipoproteinemia, and CM retention disease, respectively. These “experiments of nature” are characterized by fat malabsorption, steatorrhea, failure to thrive, low plasma levels of TGs and cholesterol, and deficiency of liposoluble vitamins and essential FAs. After summarizing and discussing the functions and regulation of these proteins for reader's comprehension, the current review focuses on their specific roles in malabsorptions and dyslipidemia-related intestinal fat hyperabsorption while dissecting the spectrum of clinical manifestations and managements. The influence of newly discovered proteins (proprotein convertase subtilisin/kexin type 9 and angiopoietin-like 3 protein) on fat absorption has also been provided. Finally, it is stressed how the overexpression or polymorphism status of the critical intracellular proteins promotes dyslipidemia and cardiometabolic disorders. |
topic |
hypobetalipoproteinemia abetalipoproteinemia chylomicron retention disease intestinal fat malabsorption apolipoprotein B-48 microsomal triglyceride transfer protein |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520312359 |
work_keys_str_mv |
AT emilelevy insightsfromhumancongenitaldisordersofintestinallipidmetabolism |
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1721504844578029568 |