Abstract
Obesity-related adipose tissue (AT) inflammation that promotes metabolic dysregulation is associated with increased AT mast cell numbers. Mast cells are potent inducers of inflammatory responses and could potentially contribute to obesity-induced AT inflammation and metabolic dysregulation. Conflicting findings were reported on obesity-related metabolic dysfunction in mast cell-deficient mice, thus creating a controversy that has not been resolved to date. Whereas traditional Kit hypomorphic mast cell-deficient strains featured reduced diet-induced obesity and diabetes, a Kit-independent model of mast cell deficiency, Cpa3Cre/+ mice, displayed no alterations in obesity and insulin sensitivity. Herein, we analyzed diet-induced obesity in Mcpt5-Cre R-DTA mice, in which the lack of mast cells is caused by a principle different from mast cell deficiency in Cpa3Cre/+ mice or Kit mutations. We observed no difference between mast cell-deficient and -proficient mice in diet-induced obesity with regards to weight gain, glucose tolerance, insulin resistance, metabolic parameters, hepatic steatosis, and AT or liver inflammation. We conclude that mast cells play no essential role in obesity and related pathologies.
Highlights
Inflammation has emerged as an important player in the pathogenesis of obesity-associated metabolic dysfunction and the development of insulin resistance and type 2 diabetes [1,2,3]
We assessed the involvement of mast cells in diet-induced obesity-related metabolic dysregulation
In contrast to KitW-sh/W-sh mice [12], but to the Cpa3Cre+ mice [16], Mcpt5-Cre+R-DTA+ mast cell-deficient and -proficient (Cre-negative R-DTA+) mice that were fed a HFD did not display any significant differences in body weight (Figure 1A), body weight gain (Figure 1B), glucose tolerance (Figure 1C), and insulin resistance (Figure 1D)
Summary
Inflammation has emerged as an important player in the pathogenesis of obesity-associated metabolic dysfunction and the development of insulin resistance and type 2 diabetes [1,2,3]. In the course of obesity, inflammatory cells, including macrophages (Mφs) and lymphocytes, accumulate in the adipose tissue (AT) and the liver [3, 4]. A switch toward the pro-inflammatory (M1) state of Mφs and increased levels of pro-inflammatory mediators, such as TNF, in the obese AT substantially contribute to insulin resistance of adipocytes [1, 5]. Identifying the exact mechanisms and cellular and molecular players governing this immune–adipose crosstalk in obesity is of particular importance. Release of pro-inflammatory mediators by mast cells can be
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