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

By Jian Liu, A. Divoux, Jiusong Sun, Jie Zhang, Karine Clément, J. Glickman, G. Sukhova, P. Wolters, Juan Du, Cem Z. Gorgun and 6 more. Nature Medicine, 2009

768 citations recorded by the source corpus.

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-γ (IFN-γ), 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.

Subfields: Epidemiology, Immunology

View Paper: https://www.semanticscholar.org/paper/29298d223c0f6836e94fb63bb22c7f1edbdc01b2

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Citations in the corpus

Adipocytokines in Obesity and Metabolic Disease (2014, positive): “Following macrophages, nearly every major type of immune cell has been identified in adipose tissue in recent years (Feuerer et al. 2009, Liu et al. 2009, Winer et al. 2009, Wu et al. 2011) and is actively involved in the endocrine function of adipose tissue in systemic metabolic regulation.”
Mechanisms and Metabolic Implications of Regional Differences among Fat Depots (2013, background): “T lymphocyte subsets, mast cells, and humoral immune-response elements are involved in the fat-tissue inflammation associated with obesity (Liu et al., 2009; Nishimura et al., 2009).”
INFLAMMATION AND LIPID SIGNALING IN THE ETIOLOGY OF INSULIN RESISTANCE (2012, neutral): “…tissue and their activation state are influenced by other immune cell types that populate obese adipose tissue, including T cells, B cells, eosinophils, and mast cells (Feuerer et al., 2009; Kintscher et al., 2008; Liu et al., 2009; Nishimura et al., 2009; Winer et al., 2011; Wu et al., 2011).”
Hypoxia and adipose tissue function and dysfunction in obesity. (2013, background): “Mast cells may be of particular importance to the innate immune response within the tissue (115).”
Adipose Tissue Distribution, Inflammation and Its Metabolic Consequences, Including Diabetes and Cardiovascular Disease (2020, background): “B-cells and mast cells also are increased in adipose tissue in the obese state (227, 236, 237).”
Cellular and Molecular Players in Adipose Tissue Inflammation in the Development of Obesity-induced Insulin Resistance (2013, positive): “Interestingly, the reconstitution of these mice with mast cells from Il6 or Ifng knockout mice did not increase insulin resistance, which suggests that IL-6 and IFN-γ from mast cells play an important role in the ability of mast cells to regulate metabolism [79].”
Macrophage death and defective inflammation resolution in atherosclerosis (2009, background): “Moreover, it will be interesting to assess the roles of mast cells and neutrophils in normal and defective inflammation resolution, because studies are increasingly implicating these two cell types in atherogenesis and plaque progressio”