Crosstalk Between Mast Cells and Adipocytes in Physiologic and Pathologic Conditions

Komi, Daniel Elieh Ali; Shafaghat, Farzaneh; Christian, Mark

doi:10.1007/s12016-020-08785-7

Cited by 37 publications

(24 citation statements)

References 88 publications

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“…Among the various resident cellular targets for leptin stimulation in vivo , we identified mast cells as a key cell population. Importantly, our results identify mast cells as modulators of leptin-driven eosinophilic reaction are in line with recent postulations that adipose tissue resident mast cells or the obesity-related increased mast cell population are modulators of adipose tissue homeostasis and inflammation ( 60 , 61 ).…”

Section: Discussionsupporting

confidence: 91%

Leptin Elicits In Vivo Eosinophil Migration and Activation: Key Role of Mast Cell-Derived PGD2

et al. 2020

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Eosinophils are key regulators of adipose tissue homeostasis, thus characterization of adipose tissue-related molecular factors capable of regulating eosinophil activity is of great interest. Leptin is known to directly activate eosinophils in vitro, but leptin ability of inducing in vivo eosinophilic inflammatory response remains elusive. Here, we show that leptin elicits eosinophil influx as well as its activation, characterized by increased lipid body biogenesis and LTC 4 synthesis. Such leptin-triggered eosinophilic inflammatory response was shown to be dependent on activation of the mTOR signaling pathway, since it was (i) inhibited by rapamycin pre-treatment and (ii) reduced in PI3K-deficient mice. Local infiltration of activated eosinophils within leptin-driven inflammatory site was preceded by increased levels of classical mast cell-derived molecules, including TNFa, CCL5 (RANTES), and PGD 2. Thus, mice were pre-treated with a mast cell degranulating agent compound 48/80 which was capable to impair leptin-induced PGD 2 release, as well as eosinophil recruitment and activation. In agreement with an indirect mast celldriven phenomenon, eosinophil accumulation induced by leptin was abolished in TNFR-1 deficient and also in HQL-79-pretreated mice, but not in mice pretreated with neutralizing antibodies against CCL5, indicating that both typical mast cell-driven signals TNFa and PGD 2 , but not CCL5, contribute to leptin-induced eosinophil influx. Distinctly, leptininduced eosinophil lipid body (lipid droplet) assembly and LTC 4 synthesis appears to depend on both PGD 2 and CCL5, since both HQL-79 and anti-CCL5 treatments were able to inhibit these eosinophil activation markers. Altogether, our data show that leptin triggers eosinophilic inflammation in vivo via an indirect mechanism dependent on activation of resident mast cell secretory activity and mediation by TNFa, CCL5, and specially PGD 2 .

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Section: Discussionsupporting

confidence: 91%

Leptin Elicits In Vivo Eosinophil Migration and Activation: Key Role of Mast Cell-Derived PGD2

et al. 2020

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“…So, further experiments demonstrated that c-kit ablation but not mast cell depletion is what improves the metabolic profile in mice (53). Although more genetic models explored the effect of the absence of mast cells in WAT, the current evidence is that it does not protect from obesity and insulin resistance (54,55). In a nutshell, mast cells are not critical players driving adipose tissue inflammation in patients with T2D.…”

Section: Discussionmentioning

confidence: 99%

In Patients With Obesity, the Number of Adipose Tissue Mast Cells Is Significantly Lower in Subjects With Type 2 Diabetes

et al. 2021

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Type 2 diabetes (T2D) is a rising global health problem mainly caused by obesity and a sedentary lifestyle. In healthy individuals, white adipose tissue (WAT) has a relevant homeostatic role in glucose metabolism, energy storage, and endocrine signaling. Mast cells contribute to these functions promoting WAT angiogenesis and adipogenesis. In patients with T2D, inflammation dramatically impacts WAT functioning, which results in the recruitment of several leukocytes, including monocytes, that enhance this inflammation. Accordingly, the macrophages population rises as the WAT inflammation increases during the T2D status worsening. Since mast cell progenitors cannot arrive at WAT, the amount of WAT mast cells depends on how the new microenvironment affects progenitor and differentiated mast cells. Here, we employed a flow cytometry-based approach to analyze the number of mast cells from omental white adipose tissue (o-WAT) and subcutaneous white adipose tissue (s-WAT) in a cohort of 100 patients with obesity. Additionally, we measured the number of mast cell progenitors in a subcohort of 15 patients. The cohort was divided in three groups: non-T2D, pre-T2D, and T2D. Importantly, patients with T2D have a mild condition (HbA1c <7%). The number of mast cells and mast cell progenitors was lower in patients with T2D in both o-WAT and s-WAT in comparison to subjects from the pre-T2D and non-T2D groups. In the case of mast cells in o-WAT, there were statistically significant differences between non-T2D and T2D groups (p = 0.0031), together with pre-T2D and T2D groups (p=0.0097). However, in s-WAT, the differences are only between non-T2D and T2D groups (p=0.047). These differences have been obtained with patients with a mild T2D condition. Therefore, little changes in T2D status have a huge impact on the number of mast cells in WAT, especially in o-WAT. Due to the importance of mast cells in WAT physiology, their decrease can reduce the capacity of WAT, especially o-WAT, to store lipids and cause hypoxic cell deaths that will trigger inflammation.

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“…Mast cells infiltrate the adipose tissue in the early stage of obesity and influence adipocytes behavior and function by secreting IFN-ϒ and IL-6 [ 50 , 51 ]. The dendritic cells, which are professional antigen-presenting cells, may stimulate Th17 response by aiding in the chemoattraction of macrophages and neutrophils in the obese adipose tissues [ 52 ].…”

Section: Inflammation As a Part Of Obesitymentioning

confidence: 99%

COVID-19 severity in obese patients: Potential mechanisms and molecular targets for clinical intervention

Sharma

Yadav

2021

Obesity Research & Clinical Practice

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Crosstalk Between Mast Cells and Adipocytes in Physiologic and Pathologic Conditions

Cited by 37 publications

References 88 publications

Leptin Elicits In Vivo Eosinophil Migration and Activation: Key Role of Mast Cell-Derived PGD2

Leptin Elicits In Vivo Eosinophil Migration and Activation: Key Role of Mast Cell-Derived PGD2

In Patients With Obesity, the Number of Adipose Tissue Mast Cells Is Significantly Lower in Subjects With Type 2 Diabetes

COVID-19 severity in obese patients: Potential mechanisms and molecular targets for clinical intervention

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