Cytokine secretion by human adipocytes is differentially regulated by adiponectin, AICAR, and troglitazone.
Adipose tissue is an active endocrine organ producing a variety of cytokines and chemokines, which may be involved in the deregulation of glucose and lipid homeostasis as well as in the inflammatory state observed in obesity. We have shown previously that differentiated human adipocytes secrete a variety of cytokines which are able to induce skeletal muscle insulin resistance. However, the regulation of these factors by anti-diabetic drugs has remained mainly undefined. Secretion of IL-6, IL-8, MIP-1alpha/beta, and MCP-1 by adipocytes was found to be downregulated by adiponectin. In parallel to adiponectin, the AMPK activator AICAR also decreased the secretion of most of the measured cytokines including IL-6 and MIP-1alpha/beta but not IL-8. In contrast, the thiazolidinedione troglitazone only slightly reduced cytokine secretion despite increasing the phosphorylation of AMPK. In conclusion, we show that adipocyte secretion is strongly inhibited by the anti-diabetic adipocyte hormone adiponectin, an effect that can also be mimicked by the AMPK activator AICAR. However, the PPARgamma agonist troglitazone is much less effective in reducing cytokine secretion.
Sell
Henrike
H
Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Düsseldorf, Germany.
Dietze-Schroeder
Daniela
D
Eckardt
Kristin
K
Eckel
Jürgen
J
D055372:AMP-Activated Protein Kinases; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D052242:Adiponectin / Q000494:pharmacology*; D000328:Adult; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012265:Ribonucleotides / Q000494:pharmacology*; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone
D052242:Adiponectin; D002839:Chromans; D016207:Cytokines; D009097:Multienzyme Complexes; D012265:Ribonucleotides; D045162:Thiazolidinediones; D000620:Aminoimidazole Carboxamide; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; D000077288:Troglitazone