Changes in adipose tissue cellular composition during obesity and aging as a cause of metabolic dysregulation

Abstract

Adipose tissue represents complex endocrine organ containing several different cellular populations including adipocytes, pre-adipocytes, mesenchymal stem cells, macrophages and lymphocytes. It is well establishing that these populations are not static but alter during obesity and aging. Changes in cellular populations alter inflammatory status and other common metabolic complications arise, therefore adipose tissue cellular composition helps dictate its endocrine and regulatory function. During excessive weight gain in obese individuals and as we age there is shift towards increase populations of inflammatory macrophages with a decrease of regulatory T cell. This altered cellular composition promote chronic low grade inflammation negatively affecting mesenchymal stem cell progenitor self-renewal, which result in deterioration of adipogenesis and increased cellular stress in adipocytes. All these changes promote metabolic disorders including age- or obese-related insulin resistance leading to type 2 diabetes.

Figure 1

Left Side: Young or lean have high populations of mesenchymal stem cells (MSC), increase capacity for adipogenesis promoting high insulin sensitivity and low inflammation. Right Side: Old or obese causes depletion of MSC and inhibition of adipogenesis, insulin resistance and high inflammation. Decrease of Tregs and increase of inflammatory M1 macrophages stimulate high inflammation and further inhibits self-renewal of MSC.