Sci. Signal., 18 August 2009
Obesity Thinner Without Mast Cells
Elizabeth M. Adler
Science Signaling, AAAS, Washington, DC 20005, USA
The old saying about mast cells was that they existed mainly to make people with allergies miserable; more recently, they have been implicated in various other human afflictions, including multiple sclerosis, atherosclerosis, and cancer. Now, Liu et al. find that mast cells may also play a role in obesity and diabetes. Consistent with previous studies, Liu et al. found more macrophages in the white adipose tissue (WAT) of obese than lean individuals; additionally, they found more mast cells. A line of mice that lack mature mast cells (KitW-sh/W-sh mice) gained less weight when fed a "Western diet" than did wild-type (WT) mice and had less fat. Mice injected daily with disodium cromoglycate (DSCG), which prevents mast cell degranulation, were also resistant to diet-induced obesity. Like the KitW-sh/W-sh mice, the DSCG-treated mice had lower concentrations of serum leptin than did WT controls, as well as improved glucose tolerance, insulin sensitivity, and a higher basal metabolic rate. Furthermore, DSCG treatment led to weight loss and improved glucose tolerance in WT mice with diet-induced obesity and diabetes. Noting that mast cells in WAT of obese humans and mice were frequently located near microvessels, the authors hypothesized that they might promote angiogenesis, thereby enhancing nutrient supply and leukocyte infiltration. Indeed, DSCG decreased WAT (and muscle) capillary density in obese WT mice fed a Western diet, so that it was comparable to that of lean mice (chow-fed or KitW-sh/W-sh). KitW-sh/W-sh mice and DSCG mice also showed an increase in WAT apoptosis and in the concentration of inflammatory mediators in WAT. Notably, WAT from KitW-sh/W-sh mice had decreased concentrations of cathepsin S, a protease implicated in promoting angiogenesis. KitW-sh/W-sh mice that underwent adoptive transfer of WT bone marrow–derived mast cells (BMMCs) showed increased WAT angiogenesis and became more susceptible to the adverse effects of a Western diet, whereas mice that received BMMCs lacking interleukin-6 or interferon- (which, unlike WT BMMCs, failed to stimulate adipocyte cathepsin activity) were still resistant to the effects of diet on weight, and serum concentrations of leptin, insulin, and glucose. The authors thus conclude that mast cells promote the development of diet-induced obesity and diabetes and that agents that prevent mast cell degranulation may represent a previously unrecognized therapeutic option for treating these conditions.
J. Liu, A. Divoux, J. Sun, J. Zhang, K. Clément, J. N. Glickman, G. K. Sukhova, P. J. Wolters, J. Du, C. Z. Gorgun, A. Doria, P. Libby, R. S. Blumberg, B. B. Kahn, G. S. Hotamisligil, G.-P. Shi, Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice. Nat. Med. 15, 940–945 (2009). [PubMed]
Citation: E. M. Adler, Thinner Without Mast Cells. Sci. Signal. 2, ec272 (2009).
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