Chronic treatment with growth hormone stimulates adiponectin gene expression in 3T3-L1 adipocytes.
Growth hormone (GH) is an important regulator of adiposity and systemic energy metabolism. Here, we have investigated the effects of GH on production of adiponectin, an anti-diabetic and anti-atherogenic hormone secreted exclusively from adipocytes. Analysis using real time quantitative PCR revealed that GH significantly increased adiponectin gene expression in a dose-dependent manner. Time course study showed that the expression of adiponectin gene started to increase only after 30 h of GH treatment (10(-8) M), suggesting it to be a chronic effect. GH-mediated induction of adiponectin gene expression was completely blocked by treatment with the Janus kinase2 (JAK2) inhibitor AG490 and the P38 mitogen activated protein (MAP) kinase inhibitor SB203580, while the specific inhibitors of phosphatidylinositol-3-kinase (LY294002) and p70S6 kinase (rapamycin) moderately enhanced GHs effect. Co-incubation of adipocytes with GH and the PPARgamma agonist rosiglitazone produced additive effects on induction of adiponectin gene expression. These results collectively suggest that GH increases adiponectin gene expression through the JAK2-P38 MAP kinase pathway, and that elevation of adiponectin production might represent a novel mechanism by which GH regulates systemic energy metabolism and insulin sensitivity.
Xu
Aimin
A
Department of Medicine, The University of Hong Kong, Hong Kong SAR, Hong Kong. amxu@hkucc.hku.hk
Wong
Lai Ching
LC
Wang
Yu
Y
Xu
Jian Yu
JY
Cooper
Garth J S
GJ
Lam
Karen S L
KS
D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects / Q000502:physiology*; D052242:Adiponectin; D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D019382:Human Growth Hormone / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D007700:Kinetics; D007739:L Cells; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011506:Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
D052242:Adiponectin; D007004:Hypoglycemic Agents; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D019382:Human Growth Hormone; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases