Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factor

Tontonoz, Peter; Hu, Erding; Spiegelman, Bruce M.

doi:10.1016/0092-8674(94)90006-x

Cited by 3,263 publications

(2,586 citation statements)

References 38 publications

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“…Forced expression of PPARg in the fibroblasts makes them differentiate into adipocytes. 26 The supernatant of the cells, differentiation in which was enhanced by addition of pioglitazone, potently promoted the tube formation of HUVECs. The enhancement of HGF mRNA expression in 3T3-L1 cells conditioned with pioglitazone was demonstrated by RT-PCR.…”

Section: Discussionmentioning

confidence: 98%

Hepatocyte growth factor secreted by cultured adipocytes promotes tube formation of vascular endothelial cells in vitro

et al. 2006

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Objective: Adipose tissue is closely associated with angiogenesis, but the mechanisms are not fully understood. Some of the adipocyte-derived cytokines are hypothesized to play an important role in angiogenesis. We evaluated tube formation of human umbilical vascular endothelial cells (HUVECs) cultured in type I collagen gel when overlaid with the supernatant of 3T3-L1 cell culture, and expression of tube-forming factor(s) in 3T3-L1 cells with or without pioglitazone. We also studied plasma growth factor levels in patients with type 2 diabetes mellitus treated with pioglitazone. Results and methods: The supernatant of 3T3-L1 cells increased tube formation of HUVECs by 9.03-fold of control. Reverse transcription-polymerase chain reaction showed that hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) mRNA were expressed in 3T3-L1 cells. Western blot analysis also demonstrated HGF and VEGF protein expression. When 3T3-L1 cells were treated with 100 nM small interfering RNAs (siRNAs) for HGF, the HGF mRNA and protein were suppressed. The VEGF mRNA and protein in the cells were also suppressed by siRNA for VEGF. The supernatant of 3T3-L1 cells treated with HGF siRNA suppressed tube formation of HUVECs by 61% compared with the supernatant of cells treated with control siRNA. Addition of VEGF siRNA resulted in no significant changes. The supernatant conditioned with pioglitazone further promoted the tube formation. Pioglitazone enhanced HGF mRNA expression in 3T3-L1 cells. After 12 weeks of pioglitazone treatment, the changes of plasma HGF levels in patients treated with pioglitazone were significantly higher than those in control. Conclusion: These results suggest that HGF secreted from 3T3-L1 cells may be the major factor regulating the tube formation, and agents that enhance the differentiation of adipocytes may promote tube formation of HUVECs mediated by HGF secreted by adipocytes.

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Section: Discussionmentioning

confidence: 98%

Hepatocyte growth factor secreted by cultured adipocytes promotes tube formation of vascular endothelial cells in vitro

et al. 2006

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“…(16) The transfection of fibroblastic cells with PPARg2 and its subsequent activation with ligand has been shown to be sufficient to initiate adipogenesis. (17) PPARg also acts as a molecular switch between the osteogenic and adipogenic pathways. Overexpression of PPARg2 in stromal cell lines resulted in the suppression of Runx2 while promoting their terminal differentiation to adipocyte.…”

Section: Introductionmentioning

confidence: 99%

Osteoblast-targeted overexpression of PPARγ inhibited bone mass gain in male mice and accelerated ovariectomy-induced bone loss in female mice

Cho

Yang

Her

et al. 2011

Journal of Bone and Mineral Research

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PPARg has critical role in the differentiation of mesenchymal stem cells into adipocytes while suppressing osteoblastic differentiation. We generated transgenic mice that overexpress PPARg specifically in osteoblasts under the control of a 2.3-kb procollagen type 1 promoter (Col.1-PPARg). Bone mineral density (BMD) of 6-to 14-week-old Col.1 À PPARg male mice was 8% to 10% lower than that of their wildtype littermates, whereas no difference was noticed in Col.1-PPARg female mice. Col.1-PPARg male mice exhibited decreased bone volume (45%), trabecular thickness (23%), and trabecular number (27%), with a reciprocal increase in trabecular spacing (51%). Dynamic histomorphometric analysis also revealed that bone-formation rate (42%) and mineral apposition rate (32%) were suppressed significantly in Col.1-PPARg male mice compared with their wild-type littermates. Interestingly, osteoclast number and surface also were decreased by 40% and 58%, respectively, in Col.1-PPARg male mice. In vitro whole-marrow culture for osteoclastogenesis also showed a significant decrease in osteoclast formation (approximately 35%) with the cells from Col.1-PPARg male mice, and OPG/RANKL ratio was reduced in stromal cells from Col.1-PPARg male mice. Although there was no significant difference in BMD in Col.1-PPARg female mice up to 30 weeks, bone loss was accelerated after ovariectomy compared with wild-type female mice (À3.9% versus À6.8% at 12 weeks after ovariectomy, p < .01), indicating that the effects of PPARg overexpression becomes more evident in an estrogen-deprived state in female mice. In conclusion, in vivo osteoblast-specific overexpression of PPARg negatively regulates bone mass in male mice and accelerates estrogen-deficiency-related bone loss in female mice. ß

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“…3 Three subtypes of PPAR, α , β and γ , have been described; and PPAR-γ was originally identified in adipose tissue as a factor that induces adipocyte differentiation and triglyceride synthesis. 4 Peroxisome proliferator-activated receptor-γ is also expressed in vascular tissues and leucocytes 5,6 and is thought to play an important role in the regulation of immune and inflammatory reactions. 7 Natural polyunsaturated fatty acids can activate PPAR-γ , and 15-deoxy-᭝ 12,14 -prostaglandin J 2 (15d-PGJ 2 ), a metabolite of PGD 2 , is the most specific natural agonist for PPAR-γ .…”

Section: Introductionmentioning

confidence: 99%

15‐Deoxy‐Δ^12,14‐prostaglandin J₂ inhibitsCX3CL1/fractalkine expression in human endothelial cells

Imaizumi¹,

Matsumiya

Tamo³

et al. 2002

Immunol Cell Biol

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Summary Peroxisome proliferator-activated receptor-γ (PPAR-γ ) is a member of nuclear hormone receptor superfamily, and is known to play a role in various biological processes including inflammatory responses and adipocyte differentiation. CX3CL1/fractalkine is a potent agonist for chemotaxis and adhesion of monocytes and lymphocytes. Endothelial cells produce fractalkine when stimulated with cytokines such as interleukin-1 (IL-1), tumour necrosis factor-α and interferon-γ (IFN-γ ). We herein report that 15-deoxy-᭝ 12,14 -prostaglandin J 2 (15d-PGJ 2 ), a PPAR-γ agonist, inhibits the expression of fractalkine induced by IFN-γ or IL-1 β in human endothelial cells. Agonist for PPAR-α (WY14643) or PPAR-γ (ciglitazone) did not inhibit the cytokine-induced fractalkine expression, and the effect of 15d-PGJ 2 may be independent of PPAR. 15-Deoxy-⌬ 12,14 prostaglandin J 2 also inhibited the adhesion of blood mononuclear cells to endothelial monolayers treated with IFN-γ or IL-1 β . The data suggest that 15d-PGJ 2 regulates inflammatory reactions, at least in part, through the inhibition of fractalkine expression and leucocyte traffic through the endothelium.

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Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factor

Cited by 3,263 publications

References 38 publications

Hepatocyte growth factor secreted by cultured adipocytes promotes tube formation of vascular endothelial cells in vitro

Hepatocyte growth factor secreted by cultured adipocytes promotes tube formation of vascular endothelial cells in vitro

Osteoblast-targeted overexpression of PPARγ inhibited bone mass gain in male mice and accelerated ovariectomy-induced bone loss in female mice

15‐Deoxy‐Δ^12,14‐prostaglandin J₂ inhibitsCX3CL1/fractalkine expression in human endothelial cells

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Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factor

Cited by 3,263 publications

References 38 publications

Hepatocyte growth factor secreted by cultured adipocytes promotes tube formation of vascular endothelial cells in vitro

Hepatocyte growth factor secreted by cultured adipocytes promotes tube formation of vascular endothelial cells in vitro

Osteoblast-targeted overexpression of PPARγ inhibited bone mass gain in male mice and accelerated ovariectomy-induced bone loss in female mice

15‐Deoxy‐Δ12,14‐prostaglandin J2 inhibitsCX3CL1/fractalkine expression in human endothelial cells

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15‐Deoxy‐Δ^12,14‐prostaglandin J₂ inhibitsCX3CL1/fractalkine expression in human endothelial cells