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- Title
Pik3r1 Is Required for Glucocorticoid-Induced Perilipin 1 Phosphorylation in Lipid Droplet for Adipocyte Lipolysis.
- Authors
Taiyi Kuo; Tzu-Chieh Chen; Lee, Rebecca A.; Nguyen Huynh Thao Nguyen; Broughton, Augusta E.; Danyun Zhang; Jen-Chywan Wang; Kuo, Taiyi; Chen, Tzu-Chieh; Thao Nguyen, Nguyen Huynh; Zhang, Danyun; Wang, Jen-Chywan; Nguyen, Nguyen Huynh Thao
- Abstract
Glucocorticoids promote lipolysis in white adipose tissue (WAT) to adapt to energy demands under stress, whereas superfluous lipolysis causes metabolic disorders, including dyslipidemia and hepatic steatosis. Glucocorticoid-induced lipolysis requires the phosphorylation of cytosolic hormone-sensitive lipase (HSL) and perilipin 1 (Plin1) in the lipid droplet by protein kinase A (PKA). We previously identified Pik3r1 (also called p85α) as a glucocorticoid receptor target gene. Here, we found that glucocorticoids increased HSL phosphorylation, but not Plin1 phosphorylation, in adipose tissue-specific Pik3r1-null (AKO) mice. Furthermore, in lipid droplets, the phosphorylation of HSL and Plin1 and the levels of catalytic and regulatory subunits of PKA were increased by glucocorticoids in wild-type mice. However, these effects were attenuated in AKO mice. In agreement with reduced WAT lipolysis, glucocorticoid- initiated hepatic steatosis and hypertriglyceridemia were improved in AKO mice. Our data demonstrated a novel role of Pik3r1 that was independent of the regulatory function of phosphoinositide 3-kinase in mediating the metabolic action of glucocorticoids. Thus, the inhibition of Pik3r1 in adipocytes could alleviate lipid disorders caused by excess glucocorticoid exposure.
- Subjects
GLUCOCORTICOID receptors; GLUCOCORTICOIDS; PERILIPIN; PHOSPHOPROTEIN genetics; PHOSPHORYLATION; PHYSIOLOGY; LIPID metabolism; ADIPOSE tissues; ANIMAL experimentation; ESTERASES; FAT cells; FATTY acids; GENETIC disorders; GENETIC techniques; INSULIN; LIPIDS; LIPID metabolism disorders; MICE; PHOSPHOTRANSFERASES; POLYMERASE chain reaction; RESEARCH funding; WESTERN immunoblotting; DEXAMETHASONE; PHARMACODYNAMICS
- Publication
Diabetes, 2017, Vol 66, Issue 6, p1601
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db16-0831