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

Abstract

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.

In Obese Patients With Type 2 Diabetes, Mast Cells in Omental Adipose Tissue Decrease the Surface Expression of CD45, CD117, CD203c, and FcϵRI

“…Here, we demonstrate that mast cells also undergo phenotypic changes in patients with T2D. In agreement with previous results of the group ( 27 , 44 ), in T2D, mast cells are more affected in o-WAT than in s-WAT. The decrease in the surface expression of CD117 in patients with T2D can explain the reduction in the number of mast cells.…”

“…Once it was clear that mast cells are important players in metabolically healthy expansion and do not contribute to T2D we and others decided to investigate if T2D negatively affects mast cells. Previous studies of our group demonstrated that the number of mast cells decreases in patients with T2D, especially in o-WAT (27). Besides, we observed that after bariatric surgery, the number of mast cells increased 10-fold in o-WAT and 4-fold in s-WAT (44).…”

“…Additionally, little is known about mast cells in T2D in humans. Nevertheless, recently, it was observed that the number of mast cells decreases in patients with T2D ( 27 ), but there is scarce information about phenotypic changes in mast cells.…”

Mast Cells and the Pancreas in Human Type 1 and Type 2 Diabetes

“…Mast cells are highly differentiated, widely distributed cells of the innate immune system. The involvement of mast cells in diabetes is corroborated by findings indicating that these cells are associated with inflamed adipose tissue, the development of certain diabetes complications such as diabetic nephropathy, and reduced wound healing in the case of diabetic foot lesions [70][71][72][73]. In the present review we have discussed the role of mast cells in the diabetic pancreas.…”

Obesogens: How They Are Identified and Molecular Mechanisms Underlying Their Action

“…In healthy individuals, WAT plays an important role in metabolism and energy homeostasis throughout the body. However, people with obesity and type two diabetes (T2D) experience an inflammatory response in their adipose tissue, particularly in visceral white fat that contains higher levels of reactive oxidative species ( 29 , 31 ). WAT differentiation and cell functioning is primarily controlled by the peroxisome proliferator-activated receptor gamma (PPARγ), also known as the “master” regulator of adipogenesis ( 32 ).…”