Mast cells are not associated with systemic insulin resistance.
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.


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.
Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
Elisa
E
Einwallner
Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Florian W
FW
Kiefer
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, CA, USA.
Giuseppe
G
Di Caro
Institute of Molecular Biotechnology of the Austrian Academy of Science, Vienna, Austria.
Michael
M
Orthofer
Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
Nadine
N
Witzeneder
Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
Gregor
G
Hörmann
Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Bianca
B
Itariu
Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Maximilian
M
Zeyda
Institute of Molecular Biotechnology of the Austrian Academy of Science, Vienna, Austria.
Josef M
JM
Penninger
Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Thomas M
TM
Stulnig
Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
Harald
H
Esterbauer
Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria. jelena.todoric@meduniwien.ac.at.|Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, CA, USA. jelena.todoric@meduniwien.ac.at.
Jelena
J
Todoric
D052436:Adipose Tissue, White / Q000473:pathology; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D008810:Mice, Inbred C57BL; D009767:Obesity, Morbid / Q000473:pathology*; D010641:Phenotype; D013851:Thinness / Q000473:pathology; D053802:Tryptases / Q000378:metabolism
D015415:Biomarkers; D016207:Cytokines; D053802:Tryptases
Inflammation; insulin resistance; mast cells; obesity