Understanding adipose tissue cellular and adipokine function and its potential role in treatment of metabolic disease

The prevalence of metabolic diseases has increased dramatically over the last few decades. The presence of metabolic disorders predispose to significant comorbidities, such as cardiovascular disease, diabetes and stroke. Worldwide, it is estimated that cardiovascular disease accounts for 17.9 million deaths annually, with diabetes accounting for 1.5 million deaths annually. Over the last few decades, increasing evidence has revealed the importance and role of adipose tissue in the pathophysiology of metabolic disease. As increasing amounts of fat are stored, adipose tissue becomes increasingly dysfunctional, affecting its many physiological roles. Various changes occur, including alterations in adipokines (adipose tissue cytokines), adipose tissue derived hormones, and immune cell profile. Our previous studies have defined a specialised population of regulatory T cells (Tregs) that reside in visceral adipose tissue (VAT) and are critical for maintaining glucose homeostasis, insulin sensitivity and respond to various anti-diabetic, insulin-sensitizing drugs. We have discovered that VAT contains two phenotypically and functionally distinct Treg populations in murine models. Our previous studies have also established that Tregs isolated from omental adipose tissue express ST2 similar to murine VAT Tregs suggesting that mouse and human Tregs are shaped by similar signals. However, this has not been formally tested. This study aims to conclusively establish whether similar VAT Treg heterogeneity and dynamics exist in humans, paving the way for therapeutic manipulations of VAT Tregs.