Dataset Information

Elevated Pentraxin 3 in Obese Adipose Tissue Promotes Adipogenic Differentiation by Activating Neuropeptide Y Signaling.

ABSTRACT: Obesity is accompanied by chronic systemic inflammation characterized by macrophage infiltration of obese tissues, an elevated plasma level of inflammatory substances, and excessive accumulation of lipids. The pro-inflammatory factor pentraxin 3 (PTX3) is also elevated in obese tissues, suggesting its potential role in adipogenesis. We found by analyzing murine preadipocyte 3T3-L1 cells, and human adipocytes derived from mesenchymal stem cells, which locally elevated PTX3 in obese adipose tissue augments adipocyte differentiation and subsequent lipid accumulation. This occurs via the upregulation of adipogenesis-related transcription factors. PTX3 enhanced lipid accumulation in murine 3T3-L1 cells by upregulating the expression of neuropeptide Y (NPY)/NPY receptor (NPYR) expression in preadipocytes. Pharmacological inhibition by NPYR antagonists abolished these effects. NPY also promoted the production of reactive oxygen species (ROS), a known trigger of adipogenesis. NPYR antagonists as well as antioxidant N-acetylcysteine showed anti-adipogenic effects by reducing the ROS levels, indicating that PTX3 mediates adipogenesis through NPY-dependent ROS production. These findings suggest that PTX3 plays a key role in the development of obesity by enhancing adipocyte differentiation and lipid synthesis via NPY/NPYR signaling. These observations provide a mechanistic explanation for the adipogenesis mediated by PTX3.

SUBMITTER: Shin MK

PROVIDER: S-EPMC6077621 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Elevated Pentraxin 3 in Obese Adipose Tissue Promotes Adipogenic Differentiation by Activating Neuropeptide Y Signaling.

Shin Min-Kyung MK Choi Bongkun B Kim Eun-Young EY Park Ji-Eun JE Hwang Eui Seung ES Lee Hyang Ju HJ Kim Min Kyung MK Kim Ji-Eun JE Kim Seong Who SW Chang Eun-Ju EJ

Frontiers in immunology 20180730

Obesity is accompanied by chronic systemic inflammation characterized by macrophage infiltration of obese tissues, an elevated plasma level of inflammatory substances, and excessive accumulation of lipids. The pro-inflammatory factor pentraxin 3 (PTX3) is also elevated in obese tissues, suggesting its potential role in adipogenesis. We found by analyzing murine preadipocyte 3T3-L1 cells, and human adipocytes derived from mesenchymal stem cells, which locally elevated PTX3 in obese adipose tissue ...[more]

PMID: 30105036

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Project description:Mesenchymal stem cells (MSCs) are multipotent cells able to differentiate into multiple cell types, including adipocytes, osteoblasts, and chondrocytes. The role of adipose-derived stem cells (ADSCs) in cancers is significantly relevant. They seem to be involved in the promotion of tumour development and progression and relapse processes. For this reason, investigating the effects of breast cancer microenvironment on ADSCs is of high importance in order to understand the relationship between tumour cells and the surrounding stromal cells. With the current study, we aimed to investigate the specific characteristics of human ADSCs isolated from the adipose tissue of breast tumour patients. We compared ADSCs obtained from periumbilical fat (PF) of controls with ADSCs obtained from adipose tissue of breast cancer- (BC-) bearing patients. We analysed the surface antigens and the adipogenic differentiation ability of both ADSC populations. C/EBPδ expression was increased in PF and BC ADSCs induced to differentiate compared to the control while PPARγ and FABP4 expressions were enhanced only in PF ADSCs. Conversely, adiponectin expression was reduced in PF-differentiated ADSCs while it was slightly increased in differentiated BC ADSCs. By means of Oil Red O staining, we further observed an impaired differentiation capability of BC ADSCs. To investigate this aspect more in depth, we evaluated the effect of selective PPARγ activation and nutritional supplementation on the differentiation efficiency of BC ADSCs, noting that it was only with a strong differentiation stimuli that the process took place. Furthermore, we observed no response in BC ADSCs to the PPARγ inhibitor T0070907, showing an impaired activation of this receptor in adipose cells surrounding the breast cancer microenvironment. In conclusion, our study shows an impaired adipogenic differentiation capability in BC ADSCs. This suggests that the tumour microenvironment plays a key role in the modulation of the adipose microenvironment located in the surrounding tissue.

Dataset Information

Elevated Pentraxin 3 in Obese Adipose Tissue Promotes Adipogenic Differentiation by Activating Neuropeptide Y Signaling.

Publications

Elevated Pentraxin 3 in Obese Adipose Tissue Promotes Adipogenic Differentiation by Activating Neuropeptide Y Signaling.

Similar Datasets

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