title: Adiponectin reduces ER stress-induced apoptosis through PPARα transcriptional regulation of ATF2 in mouse adipose.
abstract: Adiponectin is a cytokine produced predominantly by adipose tissue and correlates with glucose and lipid homeostasis. However, the effects of adiponectin on endoplasmic reticulum (ER) stress and apoptosis of adipose tissue remain elusive. In this study, we found that tunicamycin-induced ER stress increased serum free fatty acid (FFA) and impaired glucose tolerance, elevated the mRNA levels of GRP78, Chop, ATF2 and caspase 3, but reduced adiponectin mRNA level in white adipose tissue. Moreover, ER stress-triggered adipocyte apoptosis by increasing cellular FFA level and Ca2+level. Further analysis revealed that adiponectin alleviated ER stress-induced adipocyte apoptosis by elevating peroxisome proliferator-activated receptor alpha (PPARα) mRNA level. Our data also confirmed that adiponectin reduced early apoptotic cells and blocked the mitochondrial apoptosis pathway by activating the AdipoR1/AMP-activated protein kinase (AMPK) signal pathway. In addition, PPARα bound to ATF2 promoter region and inhibited transcription of ATF2. The inhibition of adipocyte apoptosis by adiponectin was correlated with transcriptional suppression of ATF2. Furthermore, adiponectin inhibited ER stress-induced apoptosis by activating the AMPK/PKC pathway. In summary, our data demonstrate adiponectin inhibited ER stress and apoptosis of adipocyte in vivo and in vitro by activating the AMPK/PPARα/ATF2 pathway. Our study establishes that adiponectin is an important adipocytokine for preventing and treating obesity.
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Zhenjiang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Gan
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Tianjiao
authors.initials: T
authors.lastname: Wu
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Feng
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Luo
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Gu
authors.affiliation: School of Animal Biology, The University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Shimin
authors.initials: S
authors.lastname: Liu
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
mesh_terms: D051698:Activating Transcription Factor 2 / Q000235:genetics* / Q000378:metabolism; D000263:Adenylate Kinase / Q000378:metabolism; D017667:Adipocytes / Q000378:metabolism; D052242:Adiponectin / Q000494:pharmacology*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005227:Fatty Acids / Q000097:blood; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism; D047493:PPAR alpha / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: D051698:Activating Transcription Factor 2; D052242:Adiponectin; C497106:Atf2 protein, mouse; D000091342:Endoplasmic Reticulum Chaperone BiP; D005227:Fatty Acids; C000717248:Hspa5 protein, mouse; D047493:PPAR alpha; D014415:Tunicamycin; D011493:Protein Kinase C; D000263:Adenylate Kinase; D002118:Calcium