Adipose Tissue Mast Cells Promote Human Adipose Beiging in Response to Cold

Abstract

In a recent study, repeated cold application induced beiging in subcutaneous white adipose tissue (SC WAT) of humans independent of body mass index. To identify factors that promote or inhibit beiging, we performed multiplex analysis of gene expression with the Nanostring nCounter system (the probe set contained genes for specific immune cell markers, cytokines, and chemokines) on the SC WAT from lean subjects. Multiple correlations analysis identified mast cell tryptase and CCL26, a chemokine for mast cells, as genes whose change correlated positively with the change in UCP1 in SC WAT, leading to the hypothesis that mast cells promote SC WAT beiging in response to cold. We quantified mast cell recruitment into SC WAT and degranulation. Mast cells increased in number in SC WAT in lean subjects, and there was an increase in the number of degranulated mast cells in both lean subjects and subjects with obesity. We determined that norepinephrine stimulated mast cell degranulation and histamine release in vitro . In conclusion, cold stimulated adipose tissue mast cell recruitment in lean subjects and mast cell degranulation in SC WAT of all research participants independent of baseline body mass index, suggesting that mast cells promote adipose beiging through the release of histamine or other products.

Relationship of sputum mast cells with clinical and inflammatory characteristics of asthma

“…Consistent with this, we observed a numerical increase in BMI and proportion classified obese in MC high participants ( P = .061 and P = .051, respectively). MCs are increased in the white adipose tissue (WAT) of obese individuals, 46,47 and serum tryptase levels are increased in obese individuals 46 . MCs have been proposed as a potential cellular link between obesity and asthma, 48 although WAT MC‐related gene expression did not differ between asthma and non‐asthma in a study of Inuit residing in Denmark and Greenland, in contrast to IL‐6 mRNA which was increased in asthma WAT 49 .…”

Inflammatory Signaling and Brown Fat Activity

“…As degranulation positively correlates with UCP1 suggests thermogenesis and beiging enhancement through histamine and secretion of other factors (91). However, these positive associations between mast cells and thermogenesis/beiging of WAT has been challenged.…”

Crosstalk Between Mast Cells and Adipocytes in Physiologic and Pathologic Conditions

“…There is accumulating evidence supporting a role for MCs in the browning of white adipocytes. It has been found that repeated cold exposure promotes beiging of human subcutaneous WAT and it is associated with increases in adipose tissue MC recruitment [9]. Recently, Finlin et al reported that MCs release histamine in response to cold, and this mediator induces the expression of UCP1 that is capable of uncoupling mitochondrial oxidative respiration and generating heat [81].…”

“…The primary mechanism of brown and beige adipocyte activation is via the sympathetic nervous system through norepinephrine action. Importantly, it has also been reported that MCs express β-adrenergic receptors and can respond to norepinephrine to degranulate and release histamine [9]. BAT is highly vascularized with a complex network of blood vessels, and when activated, there is an increase in blood flow [82].…”

“…An increasing number of researchers have reported the accumulation of MCs in AT of obese individuals [8,9]. MCs stimulate the release of cysteinyl cathepsins from vascular cells and adipocytes to catabolize ECM protein fibronectin to support adipogenesis [10].…”