Inhibition of adipocyte differentiation by mechanical stretching through ERK-mediated downregulation of PPARγ2

Tanabe, Yuji; Koga, Masashi; Saito, Maki; Matsunaga, Yumi; Nakayama, Koichi

doi:10.1242/jcs.01207

Cited by 147 publications

(132 citation statements)

References 41 publications

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“…However, only SAPK/ JNK activation reversed TGZ-induced PPAR␥ activity. In previous studies, a number of signaling effectors, including MAPK family members, have been shown to phosphorylate PPAR␥ (41)(42)(43). PPAR␥ phosphorylation can affect its activity, including reduction in the sensitivity of PPAR␥ to its cognate ligands or affect its translocation or transactivation activity.…”

Section: Discussionmentioning

confidence: 99%

Differentiation of Human Circulating Fibrocytes as Mediated by Transforming Growth Factor-β and Peroxisome Proliferator-activated Receptor γ

Hong

Belperio

Keane

et al. 2007

Journal of Biological Chemistry

206

202

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Fibrocytes are a distinct population of fibroblast-like progenitor cells in peripheral blood that have recently been shown to possess plasticity to differentiate along mesenchymal lineages, including commitment to myofibroblast and adipocyte cells. Here, we demonstrated that transforming growth factor (TGF) ␤1 drives fibrocyte-to-myofibroblast differentiation through activating Smad2/3 and SAPK/JNK MAPK pathways, which in turn stimulates ␣-smooth muscle actin expression. We determined that SAPK/JNK signaling acts in a positive feedback loop to modulate Smad2/3 nuclear availability and Smad2/3-dependent transcription. Conversely, fibrocyte-to-adipocyte differentiation is driven by the peroxisome proliferator-activated receptor (PPAR) ␥ agonist troglitazone, which is associated with cytoplasmic lipid accumulation and induction of aP2. Treatment with troglitazone also disrupted TGF␤1-activated SAPK/JNK signaling, leading to decreased Smad2/3 transactivation activity and ␣-smooth muscle actin expression. Interestingly, TGF␤1 was demonstrated to have reciprocal inhibition on fibrocyte differentiation to adipocytes. By activating SAPK/JNK signaling, which is normally suppressed during adipogenesis, PPAR␥-dependent transactivation activity and induction of aP2 expression were disrupted. Taken together, within the context of the local microenvironmental niche, the delicate balance of PPAR␥ and TGF␤1 activation drives the selection of an adipocyte or myofibroblast differentiation pathway through SAPK/ JNK signaling.

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Section: Discussionmentioning

confidence: 99%

Differentiation of Human Circulating Fibrocytes as Mediated by Transforming Growth Factor-β and Peroxisome Proliferator-activated Receptor γ

Hong

Belperio

Keane

et al. 2007

Journal of Biological Chemistry

206

202

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“…44,45 Hyperplasia appears primarily in the commitment stages in adipose tissue development and is caused by the proliferation and differentiation of mesenchymal stem cells into preadipocytes. 46,47 Hypertrophy occurs as the result of excessive accumulation of triglycerides during the process of differentiation from preadipocytes to mature adipocytes. 48 Therefore, evo may reduce hyperplasia and hypertrophy in fat tissue through an induced inhibition of both adipocyte number and size.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effect of evodiamine alone and in combination with rosiglitazone on in vitro adipocyte differentiation and in vivo obesity related to diabetes

Bak

Kim

et al. 2009

Int J Obes

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Objective: Evodiamine (evo) has been shown to exert anti-inflammatory, antinociceptive and anticancer effects. In this study, we investigated the effects of evo alone and in combination with rosiglitazone (rosi) on in vitro adipocyte differentiation and in vivo obesity related to diabetes. Methods: Adipocyte differentiation was investigated in vitro using 3T3-L1 and C3H10T1/2 cells. To determine the degree of differentiation, Oil Red O staining and reverse transcription-PCR were carried out. Four groups of db/db mice were treated intraperitoneally once per day with vehicle, evo, rosi and evo þ rosi. The mice were killed after 14 days and the blood, liver and adipose tissue were analyzed. Results: The presence of evo or evo combined with rosi during adipogenic induction has been shown to inhibit adipocyte differentiation to a significant degree, particularly at the commitment and early induction stages. The evo and evo þ rosi groups of db/db mice evidenced significant reductions in body weight gain. The ratio of epididymal white adipocyte tissue weight to body weight of the evo group was also significantly reduced. It is important to note that in the evo þ rosi treatment, blood glucose levels were reduced to a degree similar to that of the rosi group, and plasma insulin levels were reduced significantly better than that of rosi group. Furthermore, hepatic lesions associated with fat and glycogen deposition were morphologically improved in the evo and evo þ rosi groups. Conclusion:The results of this study showed that evo exerts an inhibitory effect on in vitro adipocyte differentiation and in vivo obesity, and also an improvement effect on insulin resistance. These desirable effects of evo were noted even in the presence of rosi. These results indicate that evo improves the undesirable effects of rosi, including adipogenesis, body weight gain and hepatotoxicity, while preserving its desirable blood-glucose-lowering effect.

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“…The presence of the phosphorylated form of the other MAPK pathway effector we observed, ERK1/2, as well as an epistatic component of the pathway (c-Raf) suggests that this pathway is active in mammary fat tissue. Signaling by the ERK pathway is reportedly involved in adipocyte cellular responses to cell size sensing (113), presence of adipokines (114,115), and differentiation (116,117). Consequently activity of this pathway in mammary fat tissue is consistent with a normal physiological cycle in adipocyte growth and development.…”

Section: Tgf-␤/smadmentioning

confidence: 92%

Identification of Extracellular and Intracellular Signaling Components of the Mammary Adipose Tissue and Its Interstitial Fluid in High Risk Breast Cancer Patients

Celis

Moreira

Cabezón

et al. 2005

Molecular & Cellular Proteomics

208

164

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It has become clear that growth and progression of breast tumor cells not only depend on their malignant potential but also on factors present in the tumor microenvironment. Of the cell types that constitute the mammary stroma, the adipocytes are perhaps the least well studied despite the fact that they represent one of the most prominent cell types surrounding the breast tumor cells. There is compelling evidence demonstrating a role for the mammary fat pad in mammary gland development, and some studies have revealed the ability of fat tissue to augment the growth and ability to metastasize of mammary carcinoma cells. Very little is known, however, about which factors adipocytes produce that may orchestrate these actions and how this may come about. In an effort to shed some light on these questions, we present here a detailed proteomic analysis, using two-dimensional gel-based technology, mass spectrometry, immunoblotting, and antibody arrays, of adipose cells and interstitial fluid of fresh fat tissue samples collected from sites topologically distant from the tumors of high risk breast cancer patients that underwent mastectomy and that were not treated prior to surgery. A total of 359 unique proteins were identified, including numerous signaling molecules, hormones, cytokines, and growth factors, involved in a variety of biological processes such as signal transduction and cell communication; energy metabolism; protein metabolism; cell growth and/or maintenance; immune response; transport; regulation of nucleobase, nucleoside, and nucleic acid metabolism; and apoptosis. Apart from providing a comprehensive overview of the mammary fat proteome and its interstitial fluid, the results offer some insight as to the role of adipocytes in the breast tumor microenvironment and provide a first glance of their molecular cellular circuitry. In addition, the results open new possibilities to the study of obesity, which has a strong association with type 2 diabetes, hypertension, and coronary heart disease. Molecular & Cellular Proteomics 4: 492-522, 2005.During the last years there have been numerous reports indicating that growth and progression of breast as well as other tumor cells depend not only on their malignant potential but also on stromal factors present in the tumor microenvironment, the insoluble extracellular matrix as well as cell-cell interactions (Refs.

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Inhibition of adipocyte differentiation by mechanical stretching through ERK-mediated downregulation of PPARγ2

Cited by 147 publications

References 41 publications

Differentiation of Human Circulating Fibrocytes as Mediated by Transforming Growth Factor-β and Peroxisome Proliferator-activated Receptor γ

Differentiation of Human Circulating Fibrocytes as Mediated by Transforming Growth Factor-β and Peroxisome Proliferator-activated Receptor γ

Inhibitory effect of evodiamine alone and in combination with rosiglitazone on in vitro adipocyte differentiation and in vivo obesity related to diabetes

Identification of Extracellular and Intracellular Signaling Components of the Mammary Adipose Tissue and Its Interstitial Fluid in High Risk Breast Cancer Patients

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