title: GH is a positive regulator of tumor necrosis factor alpha-induced adipose related protein in 3T3-L1 adipocytes.
abstract: Tumor necrosis factor (TNF) alpha-induced adipose-related protein (TIARP) has recently been cloned as a TNFalpha-stimulated protein expressed in adipocytes. Its expression is differentiation-dependent and potentially involved in mediating TNFalpha-induced insulin resistance. To further characterize regulation of TIARP gene expression, 3T3-L1 adipocytes were treated with key hormones modulating insulin sensitivity and influencing adipocyte metabolism, and TIARP gene expression was determined by quantitative real-time RT-PCR. Interestingly, TIARP mRNA expression was stimulated almost 9-fold after 500 ng/ml GH were added for 16 h whereas addition of 10 microM isoproterenol, 100 nM insulin and 100 nM dexamethasone for 16 h significantly decreased TIARP gene expression to between 35 and 50% of control levels. In contrast, angiotensin 2 (10 microM) and triiodothyronine (1 microM) did not have any effect. The stimulatory effect of GH was time- and dose-dependent with stimulation occurring as early as 1 h after effector addition and at concentrations as low as 5 ng/ml GH. Moreover, pharmacological inhibition of Janus kinase 2 and p42/44 mitogen-activated protein kinase reversed the stimulatory effect of GH, suggesting that both signaling molecules are involved in activation of TIARP gene expression by GH. Furthermore, an increase of TIARP mRNA could be completely reversed to control levels by withdrawal of GH for 24 h. Taken together, these results show that TIARP is not only responsive to TNFalpha but also to important other hormones influencing glucose homeostasis and adipocyte metabolism. Thus, this factor may play an integrative role in the pathogenesis of insulin resistance and its link to obesity.
authors.affiliation: Department of Internal Medicine III, University of Leipzig, 04103 Leipzig, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Fasshauer
authors.forename: J
authors.initials: J
authors.lastname: Klein
authors.forename: S
authors.initials: S
authors.lastname: Krahlisch
authors.forename: U
authors.initials: U
authors.lastname: Lössner
authors.forename: M
authors.initials: M
authors.lastname: Klier
authors.forename: M
authors.initials: M
authors.lastname: Blüher
authors.forename: R
authors.initials: R
authors.lastname: Paschke
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015153:Blotting, Western / Q000379:methods; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D013006:Growth Hormone / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D053614:Janus Kinase 2; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013268:Stimulation, Chemical
chemical_list: D000318:Adrenergic beta-Agonists; D000893:Anti-Inflammatory Agents; D007328:Insulin; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C436323:Tiarp protein, mouse; D003907:Dexamethasone; D013006:Growth Hormone; D011505:Protein-Tyrosine Kinases; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2; D019950:Mitogen-Activated Protein Kinase 1; D007545:Isoproterenol