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Characterization of Lipid Droplets i...

Kuo, Yu-Ting Andrew.

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Characterization of Lipid Droplets in Endothelium: Regulation of cAMP-mediated Lipolysis via Caveolin-1.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Characterization of Lipid Droplets in Endothelium: Regulation of cAMP-mediated Lipolysis via Caveolin-1./
Author:	Kuo, Yu-Ting Andrew.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2016,
Description:	127 p.
Notes:	Source: Dissertation Abstracts International, Volume: 77-12(E), Section: B.
Contained By:	Dissertation Abstracts International77-12B(E).
Subject:	Cellular biology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10155955
ISBN:	9781369110166

Characterization of Lipid Droplets in Endothelium: Regulation of cAMP-mediated Lipolysis via Caveolin-1.
Kuo, Yu-Ting Andrew.

Characterization of Lipid Droplets in Endothelium: Regulation of cAMP-mediated Lipolysis via Caveolin-1. - Ann Arbor : ProQuest Dissertations & Theses, 2016 - 127 p.

Source: Dissertation Abstracts International, Volume: 77-12(E), Section: B.

Thesis (Ph.D.)--Yale University, 2016.

This item is not available from ProQuest Dissertations & Theses.

Lipid droplets (LD) are intracellular compartments that serve as fat reservoirs in almost all eukaryotic cells. In mammals, LD are predominantly expressed in fat storing cells such as adipocytes and hepatocytes. Growing evidence suggests that the appearance of LD in non-fat storing cells are involved in many pathological conditions such as obesity, diabetes and atherosclerosis. Macrophages engulf oxidized low-density lipoproteins (oxLDL) and store them in LD, resulting in foam cell mice reflects the dynamic nature of LD synthesis and metabolism, implicating formation in the development of atherosclerosis. Another key cell type involved in atherosclerosis is the endothelium. Endothelial cells (EC) line the inner layer of blood vessels and are constantly exposed to high concentrations of lipoproteins and fatty acids (FA). Therefore, maintaining lipid homeostasis could be critical for EC survival and function. LD have not yet, however, been characterized in EC. My thesis demonstrates for the first time LD formation in vivo, ex vivo and in cultured EC. Importantly, the transient presence of LD-in EC after a gavage feeding of olive oil reflects the dynamic nature of LD biogenesis, implicating the physiological significance of LD in EC.

ISBN: 9781369110166Subjects--Topical Terms:

3172791
Cellular biology.

Characterization of Lipid Droplets in Endothelium: Regulation of cAMP-mediated Lipolysis via Caveolin-1.
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100 1 $a Kuo, Yu-Ting Andrew. $3 3285941
245 1 0 $a Characterization of Lipid Droplets in Endothelium: Regulation of cAMP-mediated Lipolysis via Caveolin-1.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2016
300 $a 127 p.
500 $a Source: Dissertation Abstracts International, Volume: 77-12(E), Section: B.
500 $a Adviser: William C. Sessa.
502 $a Thesis (Ph.D.)--Yale University, 2016.
506 $a This item is not available from ProQuest Dissertations & Theses.
520 $a Lipid droplets (LD) are intracellular compartments that serve as fat reservoirs in almost all eukaryotic cells. In mammals, LD are predominantly expressed in fat storing cells such as adipocytes and hepatocytes. Growing evidence suggests that the appearance of LD in non-fat storing cells are involved in many pathological conditions such as obesity, diabetes and atherosclerosis. Macrophages engulf oxidized low-density lipoproteins (oxLDL) and store them in LD, resulting in foam cell mice reflects the dynamic nature of LD synthesis and metabolism, implicating formation in the development of atherosclerosis. Another key cell type involved in atherosclerosis is the endothelium. Endothelial cells (EC) line the inner layer of blood vessels and are constantly exposed to high concentrations of lipoproteins and fatty acids (FA). Therefore, maintaining lipid homeostasis could be critical for EC survival and function. LD have not yet, however, been characterized in EC. My thesis demonstrates for the first time LD formation in vivo, ex vivo and in cultured EC. Importantly, the transient presence of LD-in EC after a gavage feeding of olive oil reflects the dynamic nature of LD biogenesis, implicating the physiological significance of LD in EC.
520 $a Structural and proteomic studies have revealed that LD are phospholipid monolayer organelles coated with numerous proteins and contain neutral lipids including triglyceride (TG) and sterol esters (SE) in their cores. Proteins recruited to the surface of LD can regulate LD dynamics and function. My thesis demonstrates that EC lacking caveolin-1 (Cav-1), a LD-associated and caveolae-coat protein, exhibit impaired LD formation. Mechanistically, this impairment is due to enhanced lipolysis rather than reduced TG synthesis or fatty acid (FA) uptake. Mechanistic results suggest the absence of Cav-1 increases cAMP/PKA signaling in EC, as phosphorylation of hormone-sensitive lipase (HSL) at Ser 563 is elevated. Unexpectedly, my data suggest that prostacyclin (PGI 2) production is enhanced in Cav-1 null EC. Blockade of PGI2 production via cyclooxygenase (COX) inhibition partially rescues impaired LD formation in Cav-1 null EC, implying a unique regulation of lipolysis by Cav-1 through autocrine production of PGI2 in EC. These results document an unanticipated role of Cav-1 regulating lipolysis in non-adipose tissue.
520 $a Taken together, my thesis successfully demonstrates endothelial LD biogenesis and its role in a non-fat storing, vascular cell type. This work not only provides evidence for the significance of lipid metabolism in endothelial biology, but also delineates a unique regulation of lipolysis in EC.
590 $a School code: 0265.
650 4 $a Cellular biology. $3 3172791
690 $a 0379
710 2 $a Yale University. $3 515640
773 0 $t Dissertation Abstracts International $g 77-12B(E).
790 $a 0265
791 $a Ph.D.
792 $a 2016
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10155955