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Publication
Intestinal epithelial cell caveolin 1 regulates fatty acid and lipoprotein
cholesterol plasma levels.
Authors Otis JP, Shen MC, Quinlivan V, Anderson JL, Farber SA
Submitted By Submitted Externally on 7/25/2018
Status Published
Journal Disease models & mechanisms
Year 2017
Date Published 3/1/2017
Volume : Pages 10 : 283 - 295
PubMed Reference 28130355
Abstract Caveolae and their structural protein caveolin 1 (CAV1) have roles in cellular
lipid processing and systemic lipid metabolism. Global deletion of CAV1 in mice
results in insulin resistance and increases in atherogenic plasma lipids and
cholesterol, but protects from diet-induced obesity and atherosclerosis. Despite
the fundamental role of the intestinal epithelia in the regulation of dietary
lipid processing and metabolism, the contributions of CAV1 to lipid metabolism
in this tissue have never been directly investigated. In this study the cellular
dynamics of intestinal Cav1 were visualized in zebrafish and the metabolic
contributions of CAV1 were determined with mice lacking CAV1 in intestinal
epithelial cells (CAV1IEC-KO). Live imaging of Cav1-GFP and fluorescently
labeled caveolae cargos shows localization to the basolateral and lateral
enterocyte plasma membrane (PM), suggesting Cav1 mediates transport between
enterocytes and the submucosa. CAV1IEC-KO mice are protected from the elevation
in circulating fasted low-density lipoprotein (LDL) cholesterol associated with
a high-fat diet (HFD), but have increased postprandial LDL cholesterol, total
free fatty acids (FFAs), palmitoleic acid, and palmitic acid. The increase in
circulating FAs in HFD CAV1IEC-KO mice is mirrored by decreased hepatic FAs,
suggesting a non-cell-autonomous role for intestinal epithelial cell CAV1 in
promoting hepatic FA storage. In conclusion, CAV1 regulates circulating LDL
cholesterol and several FA species via the basolateral PM of enterocytes. These
results point to intestinal epithelial cell CAV1 as a potential therapeutic
target to lower circulating FFAs and LDL cholesterol, as high levels are
associated with development of type II diabetes and cardiovascular disease.




Strains
StrainDevelopment StatusCreation MethodOptions
B6.Cg-Cav1tm2Tt Tg(Vil1-Cre)997GumPhenotyping ongoingknockout
View
B6.Cg-Cav1tm2TtPhenotyping ongoingknockin
View




Genes
SymbolDescription
Cav1caveolin, caveolae protein 1

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