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Growth hormone stimulates adipogenesis of 3T3-L1 cells through activation of the Stat5A/5B-PPARgamma pathway.
J Mol Endocrinol. 2007 Feb; 38(1-2):19-34.JM

Abstract

Growth hormone-deficient (GHD) patients show a decreased number of adipocytes, which is normalized by GH replacement, indicating an adipogenic effect of GH. However, the precise mechanisms underlying this effect remain to be clarified. In this study, we investigated the adipogenic effect of GH. GH stimulated MDI (3-isobutyl-1-methylxanthine, dexamethasone, and insulin)-induced adipogenesis of 3T3-L1 cells with early induction of peroxisome proliferator-activated receptors (PPAR)gamma2 expression. This adipogenic effect of GH was suppressed by overexpression of Stat5A mutant (Stat5A-Y694F), a transcriptional suppressor for the GH-Stat5A/5B signaling pathway, with the reduction of PPARgamma2 expression. Next, we investigated the relationship between Stat5A/5B and CCAAT/enhancer binding protein (C/EBP)beta/delta orPPARgamma in 3T3-L1 cells. Stat5A/5B stimulated C/EBPbeta- and C/EBPdelta-induced adipogenesis with enhancement of PPARgamma2 expression. In addition, Stat5A/5B enhanced the transcriptional activity of C/EBPbeta/delta in the PPARgamma gene promoter. Furthermore, Stat5A/5B stimulated PPARgamma-induced adipogenesis and enhanced the transcriptional activity of PPARgamma. These results suggest that the GH-Stat5A/5B signaling pathway stimulates adipogenesis in cooperation with C/EBPbeta/delta and PPARgamma. To completely understand the effect of GH, cDNA microarray analysis was performed to screen genes affected by GH during MDI-induced adipogenesis. Among 4277 genes, 18 and 19 genes were up- and down-regulated respectively. cDNA microarray analysis also indicated the up-regulation of PPARgamma and the modulation of expression of genes coding for growth factors or growth factor receptors, suggesting that GH stimulates adipogenesis in association with the modulation of cell growth. Thus, the GH-Stat5A/B signaling pathway stimulates adipogenesis through two distinct steps. In addition, cDNA microarray data provide us the further insights underlying the adipogenic effect of GH.

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Authors+Show Affiliations

Kawai M
Department of Pediatrics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Namba N
No affiliation info available
Mushiake S
No affiliation info available
Etani Y
No affiliation info available
Nishimura R
No affiliation info available
Makishima M
No affiliation info available
Ozono K
No affiliation info available

MeSH

3T3-L1 CellsAdipogenesisAnimalsGrowth HormoneMiceMice, Inbred C3HPPAR gammaSTAT5 Transcription FactorSignal Transduction

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17242167

Citation

Kawai, Masanobu, et al. "Growth Hormone Stimulates Adipogenesis of 3T3-L1 Cells Through Activation of the Stat5A/5B-PPARgamma Pathway." Journal of Molecular Endocrinology, vol. 38, no. 1-2, 2007, pp. 19-34.
Kawai M, Namba N, Mushiake S, et al. Growth hormone stimulates adipogenesis of 3T3-L1 cells through activation of the Stat5A/5B-PPARgamma pathway. J Mol Endocrinol. 2007;38(1-2):19-34.
Kawai, M., Namba, N., Mushiake, S., Etani, Y., Nishimura, R., Makishima, M., & Ozono, K. (2007). Growth hormone stimulates adipogenesis of 3T3-L1 cells through activation of the Stat5A/5B-PPARgamma pathway. Journal of Molecular Endocrinology, 38(1-2), 19-34.
Kawai M, et al. Growth Hormone Stimulates Adipogenesis of 3T3-L1 Cells Through Activation of the Stat5A/5B-PPARgamma Pathway. J Mol Endocrinol. 2007;38(1-2):19-34. PubMed PMID: 17242167.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Growth hormone stimulates adipogenesis of 3T3-L1 cells through activation of the Stat5A/5B-PPARgamma pathway. AU - Kawai,Masanobu, AU - Namba,Noriyuki, AU - Mushiake,Sotaro, AU - Etani,Yuri, AU - Nishimura,Riko, AU - Makishima,Makoto, AU - Ozono,Keiichi, PY - 2007/1/24/pubmed PY - 2007/4/25/medline PY - 2007/1/24/entrez SP - 19 EP - 34 JF - Journal of molecular endocrinology JO - J Mol Endocrinol VL - 38 IS - 1-2 N2 - Growth hormone-deficient (GHD) patients show a decreased number of adipocytes, which is normalized by GH replacement, indicating an adipogenic effect of GH. However, the precise mechanisms underlying this effect remain to be clarified. In this study, we investigated the adipogenic effect of GH. GH stimulated MDI (3-isobutyl-1-methylxanthine, dexamethasone, and insulin)-induced adipogenesis of 3T3-L1 cells with early induction of peroxisome proliferator-activated receptors (PPAR)gamma2 expression. This adipogenic effect of GH was suppressed by overexpression of Stat5A mutant (Stat5A-Y694F), a transcriptional suppressor for the GH-Stat5A/5B signaling pathway, with the reduction of PPARgamma2 expression. Next, we investigated the relationship between Stat5A/5B and CCAAT/enhancer binding protein (C/EBP)beta/delta orPPARgamma in 3T3-L1 cells. Stat5A/5B stimulated C/EBPbeta- and C/EBPdelta-induced adipogenesis with enhancement of PPARgamma2 expression. In addition, Stat5A/5B enhanced the transcriptional activity of C/EBPbeta/delta in the PPARgamma gene promoter. Furthermore, Stat5A/5B stimulated PPARgamma-induced adipogenesis and enhanced the transcriptional activity of PPARgamma. These results suggest that the GH-Stat5A/5B signaling pathway stimulates adipogenesis in cooperation with C/EBPbeta/delta and PPARgamma. To completely understand the effect of GH, cDNA microarray analysis was performed to screen genes affected by GH during MDI-induced adipogenesis. Among 4277 genes, 18 and 19 genes were up- and down-regulated respectively. cDNA microarray analysis also indicated the up-regulation of PPARgamma and the modulation of expression of genes coding for growth factors or growth factor receptors, suggesting that GH stimulates adipogenesis in association with the modulation of cell growth. Thus, the GH-Stat5A/B signaling pathway stimulates adipogenesis through two distinct steps. In addition, cDNA microarray data provide us the further insights underlying the adipogenic effect of GH. SN - 0952-5041 UR - https://www.unboundmedicine.com/medline/citation/17242167/Growth_hormone_stimulates_adipogenesis_of_3T3_L1_cells_through_activation_of_the_Stat5A/5B_PPARgamma_pathway_ L2 - https://jme.bioscientifica.com/doi/10.1677/jme.1.02154 DB - PRIME DP - Unbound Medicine ER -