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Publication : PAF signaling plays a role in obesity-induced adipose tissue remodeling.

First Author  Costa KA Year  2022
Journal  Int J Obes (Lond) Volume  46
Issue  1 Pages  68-76
PubMed ID  34493775 Mgi Jnum  J:330506
Mgi Id  MGI:7378616 Doi  10.1038/s41366-021-00961-9
Citation  Costa KA, et al. (2022) PAF signaling plays a role in obesity-induced adipose tissue remodeling. Int J Obes (Lond) 46(1):68-76
abstractText  BACKGROUND/OBJECTIVES: Platelet-activating factor receptor (PAFR) activation controls adipose tissue (AT) expansion in animal models. Our objective was twofold: (i) to check whether PAFR signaling is involved in human obesity and (ii) investigate the PAF pathway role in hematopoietic or non-hematopoietic cells to control adipocyte size. MATERIALS/SUBJECTS AND METHODS: Clinical parameters and adipose tissue gene expression were evaluated in subjects with obesity. Bone marrow (BM) transplantation from wild-type (WT) or PAFR(-/-) mice was performed to obtain chimeric PAFR-deficient mice predominantly in hematopoietic or non-hematopoietic-derived cells. A high carbohydrate diet (HC) was used to induce AT remodeling and evaluate in which cell compartment PAFR signaling modulates it. Also, 3T3-L1 cells were treated with PAF to evaluate fat accumulation and the expression of genes related to it. RESULTS: PAFR expression in omental AT from humans with obesity was negatively correlated to different corpulence parameters and more expressed in the stromal vascular fraction than adipocytes. Total PAFR(-/-) increased adiposity compared with WT independent of diet-induced obesity. Differently, WT mice receiving PAFR(-/-)-BM exhibited similar adiposity gain as WT chimeras. PAFR(-/-) mice receiving WT-BM showed comparable augmentation in adiposity as total PAFR(-/-) mice, demonstrating that PAFR signaling modulates adipose tissue expansion through non-hematopoietic cells. Indeed, the PAF treatment in 3T3-L1 adipocytes reduced fat accumulation and expression of adipogenic genes. CONCLUSIONS: Therefore, decreased PAFR signaling may favor an AT accumulation in humans and animal models. Importantly, PAFR signaling, mainly in non-hematopoietic cells, especially in adipocytes, appears to play a significant role in regulating diet-induced AT expansion.
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