title: Differential regulation of TNF receptor 1 and receptor 2 in adiponectin expression following myocardial ischemia.
abstract: BACKGROUND
  In vitro experiments demonstrate that adiponectin, a cardioprotective cytokine, is inhibited by tumor necrosis factor-alpha (TNFα). However, the role of TNFα in post-myocardial infarction (post-MI) adiponectin reduction remains unclear. More importantly, the TNF receptor type (TNFR1 or TNFR2) responsible for TNFα-mediated suppression of adiponectin production is unknown. The current study determined the role of TNFα in post-myocardial infarction (post-MI) adiponectin reduction, and identified the receptor type responsible for TNFα-mediated suppression of adiponectin production.
  
  
  RESULTS
  Adult male wild type (WT) and three knockout variety (TNFα(-/-), TNFR1(-/-), and TNFR2(-/-)) mice were subjected to MI via coronary artery occlusion. Histological and biochemical analyses were performed 3 and 7days post-MI. In WT mice, MI significantly increased plasma TNFα, reduced adipocyte adiponectin mRNA, and decreased plasma adiponectin levels. TNFα deletion had no significant effect upon basal adiponectin level, and partially restored adiponectin expression/production post-MI (P<0.01 vs. WT). Basal adiponectin levels were significantly increased in TNFR1(-/-) (P<0.05 vs. WT), and unchanged in TNFR2(-/-) mice. Importantly, suppressed adiponectin expression/production by MI or TNFα administration was markedly decreased by TNFR1 deletion (P<0.01 vs. WT), but exacerbated by TNFR2 deletion (P<0.05 vs. WT). Mechanistically, TNFR1 knockout significantly inhibited, whereas TNFR2 knockout further enhanced TNFα-induced mRNA and protein expression of ATF3, a transcriptional factor known to significantly inhibit adiponectin expression.
  
  
  CONCLUSIONS
  Our study demonstrates that TNFα overproduction is responsible for reduced adiponectin expression/production following MI. Furthermore, we show that TNFR1/TNFR2 exerts opposite effects upon adiponectin expression/production via differential regulation of ATF3.
authors: Department of Physiology, Shanxi Medical University, Taiyuan 030001, China; Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA 19107, United States. Electronic address: Yajing.Wang@jefferson.edu.
authors: Yajing
authors: Y
authors: Wang
authors: Jianli
authors: J
authors: Zhao
authors: Yanqing
authors: Y
authors: Zhang
authors: Wayne Bond
authors: WB
authors: Lau
authors: Li-Yuan
authors: LY
authors: Jiao
authors: Baojiang
authors: B
authors: Liu
authors: Yuexing
authors: Y
authors: Yuan
authors: Xiaoliang
authors: X
authors: Wang
authors: Ling
authors: L
authors: Tao
authors: Erhe
authors: E
authors: Gao
authors: Walter J
authors: WJ
authors: Koch
authors: Xin-Liang
authors: XL
authors: Ma
mesh_terms: D052242:Adiponectin / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017202:Myocardial Ischemia / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000096:biosynthesis / Q000235:genetics*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D052242:Adiponectin; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012313:RNA
keywords: Adiponectin; Diabetes; Receptor; Tumor necrosis factor