Adiponectin/T-cadherin system enhances exosome biogenesis and decreases cellular ceramides by exosomal release

Yoshinari Obata, Shunbun Kita, Yoshihisa Koyama, Shiro Fukuda, Hiroaki Takeda, Masatomo Takahashi, Yuya Fujishima, Hirofumi Nagao, Shigeki Masuda, Yoshimitsu Tanaka, Yuto Nakamura, Hitoshi Nishizawa, Tohru Funahashi, Barbara Ranscht, Yoshihiro Izumi, Takeshi Bamba, Eiichiro Fukusaki, Rikinari Hanayama, Shoichi Shimada, Norikazu MaedaIichiro Shimomura

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Adiponectin, an adipocyte-derived circulating protein, accumulates in vasculature, heart, and skeletal muscles through interaction with a unique glycosylphosphatidylinositol-anchored cadherin, T-cadherin. Recent studies have demonstrated that such accumulation is essential for adiponectin-mediated cardiovascular protection. Here, we demonstrate that the adiponectin/T-cadherin system enhances exosome biogenesis and secretion, leading to the decrease of cellular ceramides. Adiponectin accumulated inside multivesicular bodies, the site of exosome generation, in cultured cells and in vivo aorta, and also in exosomes in conditioned media and in blood, together with T-cadherin. The systemic level of exosomes in blood was significantly affected by adiponectin or T-cadherin in vivo. Adiponectin increased exosome biogenesis from the cells, dependently on T-cadherin, but not on AdipoR1 or AdipoR2. Such enhancement of exosome release accompanied the reduction of cellular ceramides through ceramide efflux in exosomes. Consistently, the ceramide reduction by adiponectin was found in aortas of WT mice treated with angiotensin II, but not in T-cadherin-knockout mice. Our findings provide insights into adiponectin/T-cadherin-mediated organ protection through exosome biogenesis and secretion.

Original languageEnglish
JournalJCI Insight
Volume3
Issue number8
DOIs
Publication statusPublished - Apr 19 2018

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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    Obata, Y., Kita, S., Koyama, Y., Fukuda, S., Takeda, H., Takahashi, M., Fujishima, Y., Nagao, H., Masuda, S., Tanaka, Y., Nakamura, Y., Nishizawa, H., Funahashi, T., Ranscht, B., Izumi, Y., Bamba, T., Fukusaki, E., Hanayama, R., Shimada, S., ... Shimomura, I. (2018). Adiponectin/T-cadherin system enhances exosome biogenesis and decreases cellular ceramides by exosomal release. JCI Insight, 3(8). https://doi.org/10.1172/jci.insight.99680