Peroxisome proliferator-activated receptor-gamma increases adiponectin secretion via transcriptional repression of endoplasmic reticulum chaperone protein ERp44.
Adiponectin, an adipocyte-derived hormone, is a versatile player involved in the regulation of energy homeostasis, cardiovascular disease, and diabetes. Within adipocytes, adiponectin is retained in the lumen of the endoplasmic reticulum (ER) by binding to the thiol protein ER resident protein 44 kDa (ERp44), which is apparently regulated by the activation of nuclear receptor peroxisome proliferator-activated receptor (PPAR)-gamma. However, the precise role of ERp44 in adiponectin secretion remains elusive. In the present study, we investigated the functional correlation between ERp44 and adiponectin in a pig model. The transcription of porcine ERp44 was regulated by PPARgamma, which was consistent with the finding of putative peroxisome proliferator response element sites within ERp44 promoter. Using chromatin immunoprecipitation and luciferase reporter assays, we demonstrated that the transcription of porcine ERp44 is repressed through binding of PPARgamma to a peroxisome proliferator response element site located between positions -981 and -1004 in its 5'-flanking region. In human embryonic kidney 293 cells stably transfected with cDNA encoding porcine adiponectin, the secretion of adiponectin was significantly up-regulated and the ERp44 mRNA was down-regulated observably, by either the treatment of PPARgamma agonist rosiglitazone or the overexpression of PPARgamma in these cells. Taken together, our results indicated that PPARgamma is an essential regulatory factor for the transcriptional activity of ERp44, which in turn controls the secretion of adiponectin.
Long
Qinqiang
Q
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
Lei
Ting
T
Feng
Bin
B
Yin
Changjun
C
Jin
Dan
D
Wu
Yanling
Y
Zhu
Xiaoyue
X
Chen
Xiaodong
X
Gan
Li
L
Yang
Zaiqing
Z
D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D018832:Molecular Chaperones / Q000235:genetics*; D041681:NIH 3T3 Cells; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding; D020218:Response Elements / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077154:Rosiglitazone; D034421:Sus scrofa; D013552:Swine; D045162:Thiazolidinediones / Q000494:pharmacology
D052242:Adiponectin; C451899:ERP44 protein, human; C520556:ERp44 protein, mouse; D008565:Membrane Proteins; D018832:Molecular Chaperones; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone