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Effects of exosomes from LPS-activated macrophages on adipocyte gene expression, differentiation, and insulin-dependent glucose uptake

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Abstract

Obesity is usually associated with low-grade inflammation, which determines the appearance of comorbidities like atherosclerosis and insulin resistance. Infiltrated macrophages in adipose tissue are partly responsible of this inflammatory condition. Numerous studies point to the existence of close intercommunication between macrophages and adipocytes and pay particular attention to the proinflammatory cytokines released by both cell types. However, it has been recently described that in both, circulation and tissue level, there are extracellular vesicles (including microvesicles and exosomes) containing miRNAs, mRNAs, and proteins that can influence the inflammatory response. The objective of the present research is to investigate the effect of exosomes released by lipopolysaccharide (LPS)-activated macrophages on gene expression and cell metabolism of adipocytes, focusing on the differential exosomal miRNA pattern between LPS- and non-activated macrophages. The results show that the exosomes secreted by the macrophages do not influence the preadipocyte-to-adipocyte differentiation process, fat storage, and insulin-mediated glucose uptake in adipocytes. However, exosomes induce changes in adipocyte gene expression depending on their origin (LPS- or non-activated macrophages), including genes such as CXCL5, SOD, TNFAIP3, C3, and CD34. Some of the pathways or metabolic processes upregulated by exosomes from LPS-activated macrophages are related to inflammation (complement activation, regulation of reactive oxygen species, migration and activation of leukocyte, and monocyte chemotaxis), carbohydrate catabolism, and cell activation. miR-530, chr9_22532, and chr16_34840 are more abundant in exosomes from LPS-activated macrophages, whereas miR-127, miR-143, and miR-486 are more abundant in those secreted by non-activated macrophages.

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Acknowledgements

The authors thank Maider Varela, Ana Lorente, Neira Sáinz, and Asunción Redín for their valuable help with laboratory techniques. Sistemas Genómicos is acknowledged for the miRNA-seq.

Funding

This work was supported by the CIBERobn and MINECO (AGL2013-45554-R).

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Authors and Affiliations

  1. Department of Nutrition, Food Science and Physiology, Centre for Nutrition Research, University of Navarra, c /Irunlarrea 1, 31008, Pamplona, Navarra, Spain

    Nicolás De Silva, Mirian Samblas, J. Alfredo Martínez & Fermín I. Milagro

  2. CIBERobn, Fisiopatología de la Obesidad y la Nutrición, Carlos III Health Institute, Madrid, Spain

    J. Alfredo Martínez & Fermín I. Milagro

  3. IdiSNA, Navarra Institute for Health Research, Pamplona, Spain

    J. Alfredo Martínez

  4. IMDEA Food, Madrid, Spain

    J. Alfredo Martínez

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  1. Nicolás De Silva
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  2. Mirian Samblas
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  4. Fermín I. Milagro
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Correspondence to Fermín I. Milagro.

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De Silva, N., Samblas, M., Martínez, J.A. et al. Effects of exosomes from LPS-activated macrophages on adipocyte gene expression, differentiation, and insulin-dependent glucose uptake. J Physiol Biochem 74, 559–568 (2018). https://doi.org/10.1007/s13105-018-0622-4

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  • DOI: https://doi.org/10.1007/s13105-018-0622-4

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