Cited by 796Adipokines, Inflammation, and Metabolic DiseasesMast cells and histamineAdipose Tissue and Metabolism

Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice

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Liu, Jian, Divoux, Adeline, Sun, Jiusong, Zhang, Jie, Clément, Karine, Glickman, Jonathan N, Sukhova, Galina K, Wolters, Paul J +8 more·2009·Nature Medicine

Abstract

Although mast cell functions have classically been related to allergic responses, recent studies indicate that these cells contribute to other common diseases such as multiple sclerosis, rheumatoid arthritis, atherosclerosis, aortic aneurysm and cancer. This study presents evidence that mast cells also contribute to diet-induced obesity and diabetes. For example, white adipose tissue (WAT) from obese humans and mice contain more mast cells than WAT from their lean counterparts. Furthermore, in the context of mice on a Western diet, genetically induced deficiency of mast cells, or their pharmacological stabilization, reduces body weight gain and levels of inflammatory cytokines, chemokines and proteases in serum and WAT, in concert with improved glucose homeostasis and energy expenditure. Mechanistic studies reveal that mast cells contribute to WAT and muscle angiogenesis and associated cell apoptosis and cathepsin activity. Adoptive transfer experiments of cytokine-deficient mast cells show that these cells, by producing interleukin-6 (IL-6) and interferon-gamma (IFN-gamma), contribute to mouse adipose tissue cysteine protease cathepsin expression, apoptosis and angiogenesis, thereby promoting diet-induced obesity and glucose intolerance. Our results showing reduced obesity and diabetes in mice treated with clinically available mast cell-stabilizing agents suggest the potential of developing new therapies for these common human metabolic disorders.

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  • Mast cells are abundant in obese adipose tissue and may elicit a pathogenic role in adipose tissue functionality.

    “Mast cells have recently been highlighted as another AT-associated cell type; abundant in obese AT, these inflammatory cells may elicit a pathogenic role in AT functionality (58).”

    From Adipose tissue remodeling and obesity (2011) · cites this paper as [58]

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Authors
Liu, J., Divoux, A., Sun, J., Zhang, J., Clément, K., Glickman, J. N., Sukhova, G. K., Wolters, P. J., Du, J., Gorgun, C. Z., Doria, A., Libby, P., Blumberg, R. S., Kahn, B. B., Hotamisligil, G. S., & Shi, G.-P.
Affiliations
  • Brigham and Women's Hospital (US)
  • Inserm (FR)
  • University of California, San Francisco (US)
  • Joslin Diabetes Center (US)
  • Beth Israel Deaconess Medical Center (US)
Corresponding author
Shi, Guo-Ping
Venue
Nature Medicine
Published
2009-07-26
Volume
15
Issue
8
Pages
940-945
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
OpenAlex
W2059261163
Cited by
796
References
36
Citations by year
2026: 18 · 2025: 16 · 2024: 33 · 2023: 19 · 2022: 26 · 2021: 42 · 2020: 51 · 2019: 40 · 2018: 51 · 2017: 52 · 2016: 49 · 2015: 55 · 2014: 66 · 2013: 87 · 2012: 77
FWCI
42.49
Type
journal article
Language
en
Open access
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • American Heart Association
  • Agence Nationale de la Recherche (ANR-05-PCOD-0030)
  • National Institutes of Health (5r01hl034636-23)
  • National Heart, Lung, and Blood Institute (HL67283, R37HL034636, R01HL088547, HL81090, HL60942, R01-HL034636, R01HL067283, R01HL081090, HL-88547, R01HL060942, HL-34636, R01HL075026)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P30DK057521, DK52539, P01DK056116, DK56116, R01DK052539, DK57521, R37DK044319, R01DK043051, P30DK040561)
Topics
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Keywords
mast cells, diet-induced obesity, diabetes mellitus, mast cell stabilization, mast cell deficiency, white adipose tissue, angiogenesis, cathepsins, interleukin-6, interferon-gamma, impaired glucose tolerance, energy expenditure, inflammatory cytokines
MeSH terms
Animals, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 2, Diet, Atherogenic, Cromolyn Sodium, Drug Evaluation, Preclinical, Female, Humans, Male, Mast Cells, Mice, Transgenic, Obesity, Organ Specificity, Proto-Oncogene Proteins c-kit, Mice

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