Adipose Stromal/Stem Cell-Derived Extracellular Vesicles: Potential Next-Generation Anti-Obesity Agents

Abstract

Over the last decade, several compounds have been identified for the treatment of obesity. However, due to the complexity of the disease, many pharmacological interventions have raised concerns about their efficacy and safety. Therefore, it is important to discover new factors involved in the induction/progression of obesity. Adipose stromal/stem cells (ASCs), which are mostly isolated from subcutaneous adipose tissue, are the primary cells contributing to the expansion of fat mass. Like other cells, ASCs release nanoparticles known as extracellular vesicles (EVs), which are being actively studied for their potential applications in a variety of diseases. Here, we focused on the importance of the con-tribution of ASC-derived EVs in the regulation of metabolic processes. In addition, we outlined the advantages/disadvantages of the use of EVs as potential next-generation anti-obesity agents.

Keywords: adipose stromal/stem cells (ASCs); adipose tissue; extracellular vesicles; metabolic disease/syndrome; obesity.

Figure 1

Schematic representation of the events occurring in metabolically healthy or unhealthy obese subjects. SAT-ASCs have the main function of regulating fat homeostasis in the AT, while VAT-ASC hypertrophy contributes to the onset of metabolic syndrome. Abbreviations: ASCs, adipose stromal/stem cells; SAT, subcutaneous adipose tissue; VAT, visceral adipose tissue.

Figure 2

Scheme of the activities promoted by the mTOR (mammalian target of rapamycin) system, composed of two complexes known as mTORC1 and mTORC2, and of its modulation by the phosphatidylinositol 3-kinase (PI3K) and AMP-activated protein kinase (AMPK) pathways. Rapamycin exogenously inhibits the mTOR system, mostly acting on the activities of mTORC1. Arrows drawn with dashed lines indicate that more downstream factors contribute to the final effect caused by the activation of mTORC1 and mTORC2. Abbreviation: HIF1α, hypoxia-inducible factor 1α.

Figure 3

ASC-derived EVs could exert a modulatory role on the activity of the two components (mTORC1 and mTORC2) of the mTOR system in cells of the white adipose tissue (WAT) through the release and donation of selected molecules (miRNAs, proteins). The arrow drawn with a dotted line indicates that mTORC2 modulates mTORC1′s function, probably inhibiting it. The red question mark indicates that EV-mediated activities have yet to be defined in adipocytes. Abbreviations: ASCs, adipose stromal/stem cells; EVs, extracellular vesicles; miRNAs, microRNAs.