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JCI Insight. 2018 Apr 19;3(8). pii: 99680. doi: 10.1172/jci.insight.99680. eCollection 2018 Apr 19.

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

Author information

1
Department of Metabolic Medicine.
2
Department of Adipose Management, and.
3
Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University, Osaka, Japan.
4
Division of Metabolomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
5
Department of Metabolism and Atherosclerosis, Graduate School of Medicine, Osaka University, Osaka, Japan.
6
Sanford Burnham Prebys Medical Discovery Institute, NIH-designated Cancer Center, Development, Aging and Regeneration Program, La Jolla, California, USA.
7
Department of Biotechnology, Graduate School of Engineering, Osaka University, Osaka, Japan.
8
Department of Immunology, Kanazawa University Graduate School of Medical Sciences, Ishikawa, Japan.

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.

KEYWORDS:

Adipose tissue; Cardiovascular disease; Cell Biology; Metabolism; endothelial cells

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