Exosomes and Obesity-Related Insulin Resistance

Abstract

Exosomes are extracellular vesicles, delivering signal molecules from donor cells to recipient cells. The cargo of exosomes, including proteins, DNA and RNA, can target the recipient tissues and organs, which have an important role in disease development. Insulin resistance is a kind of pathological state, which is important in the pathogeneses of type 2 diabetes mellitus (T2DM), gestational diabetes mellitus and Alzheimer's disease. Furthermore, obesity is a kind of inducement of insulin resistance. In this review, we summarized recent research advances on exosomes and insulin resistance, especially focusing on obesity-related insulin resistance. These studies suggest that exosomes have great importance in the development of insulin resistance in obesity and have great potential for use in the diagnosis and therapy of insulin resistance.

Keywords: exosomes; inflammation; insulin resistance; mesenchymal stem cell; obesity.

FIGURE 1

The formation of exosomes and intercellular interaction. Exosomes originate as intraluminal vesicles (ILVs) that form by inward budding of the limiting membrane of early endosomes. The endosomes mature into multivesicular bodies (MVBs) which fuse with the plasma membrane to release exosomes. Other MVBs fuse with lysosome, and the ILVs are degraded by lysosomes. Exosomes contain nucleic acid, protein, and lipid, the membrane of exosomes also include membrane proteins of endosomes. CD63, CD81, and CD9 are common surface biomarkers of exosomes. Exosomes target recipient cells through three ways, including direct fusion, endocytosis, and receptor-ligand interaction.

FIGURE 2

Exosome-mediated intercellular communication in obesity-related insulin resistance. Chronic inflammation exits in adipose tissue in obesity. Adipocyte-derived exosomes promote the polarization of M1 macrophages which secretes pro-inflammatory cytokines and exosomes, and the adipose tissue macrophage-derived exosomes can promote insulin resistance in adipocytes. In obesity, exosomes from adipose tissue, liver, pancreas, and muscle, mediating intra-organ cross talks or inter-organ cross talks by blood circulation. In obesity, these organs or tissues increase the secretion of exosomes that promote insulin resistance or decrease the secretion of exosomes that ameliorate insulin resistance.

FIGURE 3

MSC-derived exosomes ameliorate insulin resistance. MSC-derived exosomes down regulate blood glucose through reverse insulin resistance in insulin target tissue and relieve β cell destruction. MSC-derived exosomes also ameliorate insulin resistance by promoting M2 macrophage polarization and inhibiting M1 macrophage polarization.