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

Frontiers in Immunology

Seong Who Kim¹  Min Kyung Kim¹  Hyang Ju Lee¹  Eui Seung Hwang²  Ji-Eun Kim²  Eun-Young Kim³  Ji-Eun Park³  Eun-Ju Chang³  Min-Kyung Shin³  Bongkun Choi³ 

[1] Department of Biochemistry and Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea;Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea;Stem Cell Immunomodulation Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea;

关键词: pentraxin3;    neuropeptide Y;    obesity;    adipogenesis;    macrophage;   

DOI  :  10.3389/fimmu.2018.01790

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown