Mast cells are not associated with systemic insulin resistance

Elisa Einwallner, Florian W. Kiefer, Giuseppe Di Caro, Michael Orthofer, Nadine Witzeneder, Gregor Hörmann, Bianca Itariu, Maximilian Zeyda, Josef M. Penninger, Thomas M. Stulnig, Harald Esterbauer, Jelena Todoric

Research output: Contribution to journalArticle

Abstract

Background: Infiltration of white adipose tissue (WAT) by inflammatory cells in obesity is considered to be a key event in the development of insulin resistance. Recently, mast cells (MCs) have been identified as new players in the pathogenesis of obesity. We aimed to investigate the relationship between MCs and various inflammatory markers in serum and WAT and to determine the role of MCs in the aetiology of insulin resistance. Materials and methods: Gene expression was measured in WAT from 20 morbidly obese patients and 20 nonobese control subjects. Homoeostasis Model of Assessment-Insulin Resistance (HOMA-IR) was used to estimate insulin sensitivity. In addition, wild-type and mast cell-deficient mice were fed a high-fat or low-fat diet to study mast cell influence on inflammatory cell polarization in WAT and overall metabolic changes. Results: WAT levels of MC-specific TPSb2 transcript were increased in obesity and significantly positively correlated with TNF, CCL2, CCL5 and CD68 gene expression levels in our study subjects after adjustment for sex, age and BMI. Accordingly, MC deficiency abrogated increase in expression of pro-inflammatory M1 macrophage marker genes in mouse WAT upon high-fat diet feeding. However, MCs accumulated in obese human WAT independent of insulin resistance and systemic changes in inflammatory mediators. Conclusions: Our results suggest that MCs contribute to the local pro-inflammatory state within WAT in obesity but do not play a primary role in causing insulin resistance.

Original languageEnglish
Pages (from-to)911-919
Number of pages9
JournalEuropean Journal of Clinical Investigation
Volume46
Issue number11
DOIs
Publication statusPublished - Nov 1 2016

Keywords

  • Inflammation
  • insulin resistance
  • mast cells
  • obesity

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry
  • Clinical Biochemistry

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  • Cite this

    Einwallner, E., Kiefer, F. W., Di Caro, G., Orthofer, M., Witzeneder, N., Hörmann, G., Itariu, B., Zeyda, M., Penninger, J. M., Stulnig, T. M., Esterbauer, H., & Todoric, J. (2016). Mast cells are not associated with systemic insulin resistance. European Journal of Clinical Investigation, 46(11), 911-919. https://doi.org/10.1111/eci.12675