TY - JOUR
T1 - Prostaglandin E receptor subtype 4 regulates lipid droplet size and mitochondrial activity in murine subcutaneous white adipose tissue
AU - Ying, Fan
AU - Cai, Yin
AU - Cai, Yu
AU - Wang, Yu
AU - Tang, Eva Hoi Ching
N1 - Funding Information:
The authors thank Prof. Paul M. Vanhoutte (University of Hong Kong), for language editing and proofreading the manuscript. This work was supported, in part, by grants from the Research Grant Council of Hong Kong Special Administrative Region (SAR) under the General Research Fund (27101314 to E.H.C.T.). The authors declare no conflicts of interest.
Publisher Copyright:
© FASEB.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2017/9
Y1 - 2017/9
N2 - The purpose of this study was to investigate whether genetic ablation of prostaglandin E receptor subtype 4 (EP4) affects white adipose tissue (WAT) remodeling mediated by β3-adrenergic stimulation. The selective β3-adrenergic agonist, CL316243 (1 mg/kg/d, i.p.) caused a greater increase in metabolic rate in EP4-knockout mice. CL316243 fragmented the unilocular lipid droplet into multilocular lipid vacuoles and increased mitochondrial biogenesis and its activity. These changes were amplified in mice with EP4 deficiency and were selectively seen in subcutaneous WAT. The expression of fat-specific protein (FSP)-27, a protein that promotes fusion of triglycerides and formation of unilocular lipid droplets were diminished, whereas the expression of phosphorylated AMPK, the upstream regulator of FSP27, was enhanced in EP4-deficient mice. The present study showed that EP4 acts as a negative regulator of WAT remodeling, it tightly coordinates rates of triglyceride storage in lipid droplets and mitochondrial respiratory function in subcutaneous white adipocytes through the phosphorylated AMPK-FSP27 signaling axis. Thus, deletion of EP4 increases mitochondrial biogenesis and oxidative capacity in WAT, and fat mass loss ensues in mice.
AB - The purpose of this study was to investigate whether genetic ablation of prostaglandin E receptor subtype 4 (EP4) affects white adipose tissue (WAT) remodeling mediated by β3-adrenergic stimulation. The selective β3-adrenergic agonist, CL316243 (1 mg/kg/d, i.p.) caused a greater increase in metabolic rate in EP4-knockout mice. CL316243 fragmented the unilocular lipid droplet into multilocular lipid vacuoles and increased mitochondrial biogenesis and its activity. These changes were amplified in mice with EP4 deficiency and were selectively seen in subcutaneous WAT. The expression of fat-specific protein (FSP)-27, a protein that promotes fusion of triglycerides and formation of unilocular lipid droplets were diminished, whereas the expression of phosphorylated AMPK, the upstream regulator of FSP27, was enhanced in EP4-deficient mice. The present study showed that EP4 acts as a negative regulator of WAT remodeling, it tightly coordinates rates of triglyceride storage in lipid droplets and mitochondrial respiratory function in subcutaneous white adipocytes through the phosphorylated AMPK-FSP27 signaling axis. Thus, deletion of EP4 increases mitochondrial biogenesis and oxidative capacity in WAT, and fat mass loss ensues in mice.
KW - CL316243
KW - FSP27
KW - Mitochondrial biogenesis
KW - Phosphorylation AMPK
KW - WAT remodeling
UR - http://www.scopus.com/inward/record.url?scp=85028928075&partnerID=8YFLogxK
U2 - 10.1096/fj.201700191R
DO - 10.1096/fj.201700191R
M3 - Journal article
C2 - 28533326
AN - SCOPUS:85028928075
SN - 0892-6638
VL - 31
SP - 4023
EP - 4036
JO - FASEB Journal
JF - FASEB Journal
IS - 9
ER -