title: Pik3r1 Is Required for Glucocorticoid-Induced Perilipin 1 Phosphorylation in Lipid Droplet for Adipocyte Lipolysis.
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 calledp85α) as a glucocorticoid receptor target gene. Here, we found that glucocorticoids increased HSL phosphorylation, but not Plin1 phosphorylation, in adipose tissue-specificPik3r1-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.
authors.affiliation: Endocrinology Graduate Program, University of California, Berkeley, Berkeley, CA.|Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA.
authors.forename: Taiyi
authors.initials: T
authors.lastname: Kuo
authors.affiliation: Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA.|Metabolic Biology Graduate Program, University of California, Berkeley, Berkeley, CA.
authors.forename: Tzu-Chieh
authors.initials: TC
authors.lastname: Chen
authors.affiliation: Endocrinology Graduate Program, University of California, Berkeley, Berkeley, CA.|Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Lee
authors.affiliation: Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA.
authors.forename: Nguyen Huynh Thao
authors.initials: NHT
authors.lastname: Nguyen
authors.affiliation: Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA.
authors.forename: Augusta E
authors.initials: AE
authors.lastname: Broughton
authors.affiliation: Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA.
authors.forename: Danyun
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Endocrinology Graduate Program, University of California, Berkeley, Berkeley, CA walwang@berkeley.edu.|Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA.|Metabolic Biology Graduate Program, University of California, Berkeley, Berkeley, CA.
authors.forename: Jen-Chywan
authors.identifier: 0000-0001-6030-6886
authors.initials: JC
authors.lastname: Wang
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D058543:Class Ia Phosphatidylinositol 3-Kinase / Q000235:genetics*; D003907:Dexamethasone / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D055785:Gene Knockdown Techniques; D005938:Glucocorticoids / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D066292:Lipid Droplets / Q000187:drug effects / Q000378:metabolism*; D008066:Lipolysis; D051379:Mice; D000070778:Perilipin-1 / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D002787:Sterol Esterase / Q000187:drug effects / Q000378:metabolism
chemical_list: D005230:Fatty Acids, Nonesterified; D005938:Glucocorticoids; D007328:Insulin; D000070778:Perilipin-1; C000602979:Plin1 protein, mouse; D003907:Dexamethasone; D019869:Phosphatidylinositol 3-Kinases; D058543:Class Ia Phosphatidylinositol 3-Kinase; C000622001:Pik3r1 protein, mouse; D002787:Sterol Esterase