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.
Highlights
The incidence of diabetes has increased four-fold in the last three decades, becoming the ninth death cause worldwide [1] and will affect 693 million people by 2045 [2]
The American Diabetes Association considers that the goal for patients with type 2 diabetes (T2D) is to have their HbA1c below 7% since it considerably reduces the risk for cardiovascular disease
In sWAT (Figure 3 and Supplementary Figure 2), the differences are only between non-T2D and T2D groups (p=0.047). These results indicate that mast cells of both o-white adipose tissue (WAT) and sWAT are negatively affected by the dysregulation of glucose metabolism, when T2D is reached
Summary
The incidence of diabetes has increased four-fold in the last three decades, becoming the ninth death cause worldwide [1] and will affect 693 million people by 2045 [2]. When the caloric intake exceeds the energetic demands, adipocytes in white adipose tissue (WAT) store the excess energy as lipids, mainly triglycerides. When this positive energy imbalance continues for a long time, the WAT has to expand. Adipocytes extend WAT via hypertrophy or hyperplasia. Adipocyte hyperplasia promotes insulin sensitivity and tissue homeostasis [3, 4]. Adipocyte hypertrophy enhances insulin resistance and inflammation [3, 4]. There are differences in adipose tissue depending on the depot location, including gene expression, metabolic features, and adipokine secretion [5, 6]
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