Adipose stem cells in obesity: challenges and opportunities

Abstract

Adipose tissue, the storage of excessive energy in the body, secretes various proteins called adipokines, which connect the body's nutritional status to the regulation of energy balance. Obesity triggers alterations of quantity and quality of various types of cells that reside in adipose tissue, including adipose stem cells (ASCs; referred to as adipose-derived stem/stromal cells in vitro). These alterations in the functionalities and properties of ASCs impair adipose tissue remodeling and adipose tissue function, which induces low-grade systemic inflammation, progressive insulin resistance, and other metabolic disorders. In contrast, the ability of ASCs to recruit new adipocytes when faced with caloric excess leads to healthy adipose tissue expansion, associated with lower amounts of inflammation, fibrosis, and insulin resistance. This review focuses on recent advances in our understanding of the identity of ASCs and their roles in adipose tissue development, homeostasis, expansion, and thermogenesis, and how these roles go awry in obesity. A better understanding of the biology of ASCs and their adipogenesis may lead to novel therapeutic targets for obesity and metabolic disease.

Keywords: APCs; ASCs; adipose tissue development; homeostasis; obesity; thermogenesis.

Figure 1. Tracking adipogenesis using Mural-Trak (SMA+) fate mapping model

(A) Genetic alleles for tracing SMA cells. (B) SMA+ APCs at pulse (2 days after tamoxifen) or at chase at room temperature or cold challenged. SMA+ labeled perivascular cells can give rise to both white and beige adipocytes.

Figure 2. Schematic diagram of adipogenesis in healthy and obese states

ASCs give rise to different adipocytes. White adipocytes store energy, whereas brown and beige adipocytes are specialized for energy expenditure. Of note, transdifferentiation between beige and white adipocytes, or between brown and white adipocytes are also suggested. In addition, mature white adipocytes have the ability to dedifferentiate into multipotent ASCs. In obese state, the roles of ASCs get altered, leading to the generation of more white fat and the whitening of thermogenic brown and beige fat.