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Rab8a Deficiency in Skeletal Muscle Causes Hyperlipidemia and Hepatosteatosis by Impairing Muscle Lipid Uptake and Storage.

Authors :
Qiaoli Chen
Ping Rong
Dijin Xu
Sangsang Zhu
Liang Chen
Bingxian Xie
Qian Du
Chao Quan
Yang Sheng
Tong-Jin Zhao
Peng Li
Hong Yu Wang
Shuai Chen
Chen, Qiaoli
Rong, Ping
Xu, Dijin
Zhu, Sangsang
Chen, Liang
Xie, Bingxian
Du, Qian
Source :
Diabetes; Sep2017, Vol. 66 Issue 9, p2387-2399, 13p, 1 Color Photograph, 1 Diagram, 4 Graphs, 1 Map
Publication Year :
2017

Abstract

Skeletal muscle absorbs long-chain fatty acids (LCFAs) that are either oxidized in mitochondria or temporarily stored as triglycerides in lipid droplets (LDs). So far, it is still not fully understood how lipid uptake and storage are regulated in muscle and whether these are important for whole-body lipid homeostasis. Here we show that the small GTPase Rab8a regulates lipid uptake and storage in skeletal muscle. Muscle-specific Rab8a deletion caused hyperlipidemia and exacerbated hepatosteatosis induced by a high-fat diet. Mechanistically, Rab8a deficiency decreased LCFA entry into skeletal muscle and inhibited LD fusion in muscle cells. Consequently, blood lipid levels were elevated and stimulated hepatic mammalian target of rapamycin, which enhanced hepatosteatosis by upregulating hepatic lipogenesis and cholesterol biosynthesis. Our results demonstrate the significance of lipid uptake and storage in muscle in regulating whole-body lipid homeostasis, and they shed light on the roles of skeletal muscle in the pathogenesis of hyperlipidemia and hepatosteatosis. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00121797
Volume :
66
Issue :
9
Database :
Complementary Index
Journal :
Diabetes
Publication Type :
Academic Journal
Accession number :
124770271
Full Text :
https://doi.org/10.2337/db17-0077