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

International Journal of Obesity volume 46, pages 68–76 (2022)Cite this article

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Abstract

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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Fig. 1: PAFR expression in human WAT, adipocytes, and SVF.
Fig. 2: Effect of PAF signaling predominantly in hematopoietic or non-hematopoietic-derived cells in the adipose tissue expansion.
Fig. 3: Inflammatory alterations in the chimera groups.
Fig. 4: Effect of PAF on triglyceride accumulation and differentiation of 3T3-L1 fibroblasts.
Fig. 5: The summary of PAF signaling effect on adipose tissue in obesity.

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Acknowledgements

The authors thank Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Comité français d’Evaluation de la Coopération Universitaire et Scientifique avec le Brésil (COFECUB) grant no 88887.130206/2017-01, Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), National Council for Scientific and Technological Development (CNPq/Brazil) by financial support and National Agency of Research (Captor program). Clinical investigation was performed at the Human Nutrition Research Center (CRNH Ile de France), Pitié-Salpêtrière Hospital.

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Authors and Affiliations

  1. Immunometabolism, Department of Nutrition, Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Kátia A. Costa, Débora R. Lacerda, Ana L. M. Silveira, Laís B. Martins, Marina C. Oliveira & Adaliene V. M. Ferreira

  2. Department of Basic Nursing, Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Barbara M. Rezende

  3. Department of Microbiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Zélia Menezes-Garcia

  4. Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Fernanda L. B. Mügge, Aristóbolo M. Silva & Vanessa Pinho

  5. Immunopharmacology, Department of Immunology and Biochemistry, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Mauro M. Teixeira

  6. Sorbonne Université, INSERM, Nutrition and obesities: systemic approaches (Nutriomics), Paris, France

    Christine Rouault, Geneviève Marcelin & Karine Clément

  7. Assistance Publique Hôpitaux de Paris, Nutrition Departments, CRNH Ile de France, Pitié-Salpêtrière Hospital, Paris, France

    Christine Rouault, Geneviève Marcelin & Karine Clément

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  1. Kátia A. Costa
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Contributions

Conceptualization, AVMF; Project Administration, KAC; Methodology, AVMF, CR, GM, VPS, BMR, and AMS; Investigation, KAC, DRL, ALMS, MCO, ZMG, and FLBM; Resources, AVMF, MMT, AMS and KC; Writing – Original Draft, KAC, ALMS, and DRL; Visualization, ALMS, LBM, and MCO; Writing – Review & Editing, AVMF, GM, ALMS, MCO, AMS, KC and CR; Funding Acquisition, AVMF and KC; Guarantor of this work, AVMF.

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Correspondence to Adaliene V. M. Ferreira.

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Costa, K.A., Lacerda, D.R., Silveira, A.L.M. et al. PAF signaling plays a role in obesity-induced adipose tissue remodeling. Int J Obes 46, 68–76 (2022). https://doi.org/10.1038/s41366-021-00961-9

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