Adiponectin is partially associated with exosomes in mouse serum

Abstract

Previous studies suggest that adipocyte-derived exosomes play a role in cell-to-cell communication during the development of metabolic diseases. However, the characteristics and function of exosomes released from adipocytes in vivo remain to be elucidated. Clearly, exosomes released from adipocytes could exist in the circulation. In addition, because the composition of exosomes is heterogenic, depending on the cellular origin of the exosome, adipocyte-derived exosomes could be accompanied by molecules produced specifically in adipocytes. In this context, this study postulated that such molecules associated with exosomes in the serum could be markers for adipocyte-derived exosomes in vivo. This study particularly focused on secretory proteins produced specifically in adipocytes, namely adipocytokines including adiponectin, leptin, and resistin. Serum adiponectin is partially associated with exosomesBased on western blotting, CD63, a well-known protein marker of exosomes, was concentrated in the pellet of mouse serum after ultracentrifugation, suggesting successful isolation of exosomes. Western blotting detected adiponectin but no leptin and only trace amounts of resistin in the exosome fraction. After ultracentrifugation on a discontinuous gradient, both adiponectin and CD63 were detected in a fraction at a density of 1.17 g/mL, consistent with the density of exosomes. The adiponectin signal in the exosome fraction was decreased by proteinase K treatment and completely quenched by a combination of proteinase K and Triton X-100. These results suggest that a portion of adiponectin exists as a transmembrane protein in the exosomes in mouse serum. showed that the concentration of adiponectin in the serum and the ratio of adiponectin to total protein in the exosome fraction were lower in obese mice than in lean mice.In conclusion, this study showed that serum adiponectin is partially associated with exosomes in mice. Considering that adiponectin is produced exclusively by adipocytes, adiponectin-associated exosomes in serum could be derived from adipocytes. This study proposes that adiponectin could be a marker for exosomes released from adipocytes in vivo.iii

Effect of extracellular vesicles of human adipose tissue on insulin signaling in liver and muscle cells

“…Very recently, Phoonsawat et al . also reported adiponectin‐positive EV in mouse plasma. These data indicate that adipocyte EVs are present in plasma and may therefore be systemic communicators between AT and liver or skeletal muscle.…”

Adipose crosstalk with other cell types in health and disease

“…EVs could be successfully purified by differential centrifugation of conditioned medium obtained from cultured adipose tissue explants [15,37] or adipocyte cultures [46]. In addition, EVs obtained from mouse serum [51], differentiated 3T3-L1 cell lines [17], and rat primary adipocyte cultures [40] were found to contain fat-cell specific proteins such as aP2 and adiponectin, suggesting that mature adipocytes can contribute to EVs in circulation. Hence, secretion of EVs may be a novel means through which adipocytes communicate with distant organs and regulate whole-body metabolism under both physiologic and pathophysiologic conditions [31].…”

The Role of Bone Marrow Microenvironment in Governing the Balance between Osteoblastogenesis and Adipogenesis

“…Exosomes are membrane vesicles that carry a cargo of proteins, lipids and nuclear acids, which may differ based on adipogenic stages and/or under pathological conditions [120,121,122]. Adipocyte-secreted exosomes are demonstrated to contain specific transcripts (such as adiponectin [123] and aP2 [124]) and miRNAs [119,99], which are transported into recipient cells and are involved in modulating gene expression as well as energy metabolism. Several studies demonstrated that adipocyte derived exosomes mediate cell-cell communication that might play a role in controlling lipogenesis and cell size [121], obesity related disease [120] and nonalcoholic fatty liver disease [125].…”