Ann Pediatr Endocrinol Metab.  2016 Sep;21(3):119-125. 10.6065/apem.2016.21.3.119.

Exosomes as the source of biomarkers of metabolic diseases

• Lee MJ
• Park DH
• Kang JH

• KMID: 2366786
• DOI: http://doi.org/10.6065/apem.2016.21.3.119

Abstract

Exosomes are extracellular vesicles that contain molecules that regulate the metabolic functions of adjacent or remote cells. Recent in vitro, in vivo and clinical studies support the hypothesis that exosomes released from various cell types play roles in the progression of metabolic disorders including type 2 diabetes. Based on this concept and advances in other diseases, the proteins, mRNA, microRNA and lipids in exosomes isolated from biological fluids have been proposed as biomarkers in metabolic disorders. However, several problems with the development of clinically applicable biomarkers have not been resolved. In this review, the biologic functions of exosomes are briefly introduced, and we discuss the technical and practical pros and cons of different methods of exosome isolation for the identification of exosomal biomarkers of metabolic disorders. Standardization of preanalytical variables and isolation of high-purity exosomes from fully characterized biological fluids will be necessary for the identification of useful exosomal biomarkers that can provide insights into the pathogenic mechanisms of complications of metabolic syndrome and of whole-body metabolism.

Keyword

Exosomes; Diabetes mellitus; Biomarkers; Standardization; Metabolic syndrome X

MeSH Terms

Biomarkers*
Diabetes Mellitus
Exosomes*
Extracellular Vesicles
In Vitro Techniques
Metabolic Diseases*
Metabolic Syndrome X
Metabolism
MicroRNAs
RNA, Messenger
Biomarkers
MicroRNAs
RNA, Messenger

Figure

• 

  Fig. 1 Biogenesis and secretion of exosomes. Exosomes originate from the endolysosomal pathway and exhibit a homogeneous size and shape. During the maturation of the early endosome, the inward budding of cellular compartments that occurs in the membrane of the endosome produces multivesicular bodies (MVBs). The internal vesicles (intraluminal vesicles; ILVs) within MVBs contain soluble proteins, transmembrane proteins, lipids, receptors, ligands, mRNAs and miRNAs lower inserted box that are responsible for intercellular communication. The internal sorting of these molecules is precisely regulated by several mechanisms including the endosomal sorting complexes required for transport system. MVBs can fuse with lysosomes to recycle the contents of the ILVs or with the plasma membrane to release ILVs as exosomes. The mechanisms that decide between the release of MVBs as exosomes or their allocation to recycling pathways are not fully understood. GPI, glycophosphatidylinositol; TM, transmembrane.

• 

  Fig. 2 Electron microscopic image of exosomes prepared from cell culture media (CM). After full differentiation of murine myoblast (C2C12 cells) to myocytes, exosomes were isolated from CM by differential ultracentrifugation. (A, B) Small vesicles (white arrows) homogeneously sized <150 nm are clearly identifiable. (C, D) Several aggregated vesicles are also observed when ultracentrifugation is used to prepare exosomes. Arrowheads and asterisk indicate membrane of exosome and exosomal body, respectively.

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