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

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

doi:10.1172/jci.insight.99680

Cited by 145 publications

(184 citation statements)

References 74 publications

(91 reference statements)

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“…Toxic sphingolipids such as sulfatides or psychosine have been shown to accumulate in some sphingolipidoses and to be secreted with EVs . The cellular ceramide content has also been shown to be regulated by exosome secretion through adiponectin binding to T‐cadherin . Adiponectin is a protein secreted by adipocytes as oligomers that bind to T‐cadherin, a unique GPI‐anchored form of cadherin notably present in lipid rafts of endothelial vascular cells.…”

Section: Exosomes and Homeostasismentioning

confidence: 99%

“…118,119 The cellular ceramide content has also been shown to be regulated by exosome secretion through adiponectin binding to Tcadherin. 120 Adiponectin is a protein secreted by adipocytes as oligomers that bind to T-cadherin, a unique GPI-anchored form of cadherin notably present in lipid rafts of endothelial vascular cells. It was shown that high molecular weight multimeric adiponectin accumulates in MVE ILVs, stimulates exosome biogenesis and exosomal release of ceramides, with a concomitant reduction in cellular ceramides both in vitro and in vivo.…”

Section: Lipidsmentioning

confidence: 99%

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Exosomes: Revisiting their role as “garbage bags”

Vidal

2019

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123

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In recent years, the term “extracellular vesicle” (EV) has been used to define different types of vesicles released by various cells. It includes plasma membrane‐derived vesicles (ectosomes/microvesicles) and endosome‐derived vesicles (exosomes). Although it remains difficult to evaluate the compartment of origin of the two kinds of vesicles once released, it is critical to discriminate these vesicles because their mode of biogenesis is probably directly related to their physiologic function and/or to the physio‐pathologic state of the producing cell. The purpose of this review is to specifically consider exosome secretion and its consequences in terms of a material loss for producing cells, rather than on the effects of exosomes once they are taken up by recipient cells. I especially describe one putative basic function of exosomes, that is, to convey material out of cells for off‐site degradation by recipient cells. As illustrated by some examples, these components could be evacuated from cells for various reasons, for example, to promote “differentiation” or enhance homeostatic responses. This basic function might explain why so many diseases have made use of the exosomal pathway during pathogenesis.

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Section: Exosomes and Homeostasismentioning

confidence: 99%

Section: Lipidsmentioning

confidence: 99%

Exosomes: Revisiting their role as “garbage bags”

Vidal

2019

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123

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“…This group showed exosome release is attenuated after inhibition of the sphingomyelin (SM) hydrolyzing enzyme neutral sphingomyelinase . Obata et al showed cellular CER levels decreased when adiponectin mediated increase in exosome biogenesis and secretion occurs …”

Section: Introductionmentioning

confidence: 99%

“…26 Obata et al showed cellular CER levels decreased when adiponectin mediated increase in exosome biogenesis and secretion occurs. 27 Urinary lipidomics, in general, has become an attractive area in biomedical sciences since the urine is a rich source of non-invasive biomarkers and it can be used to investigate disease mechanisms. Lipidomics of urinary exosomes may offer an additional advantage because the packaged cargo within these urinary exosomes may be associated with alterations in various cellular processes including signaling, differentiation, and communication.…”

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confidence: 99%

Lipidomic analysis of urinary exosomes from hereditary α‐tryptasemia patients and healthy volunteers

et al. 2019

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Exosomes are nano‐sized vesicles that are involved in various biological processes including cell differentiation, proliferation, signaling, and intercellular communication. Urinary exosomes were isolated from a cohort of hereditary α‐tryptasemia (HαT) patients and from healthy volunteers. There was a greater number of exosomes isolated from the urine in the HαT group compared to the control volunteers. Here, we investigated the differences in both lipid classes and lipid species within urinary exosomes of the two groups. Lipids were extracted from urinary exosomes and subjected to liquid chromatography mass spectrometry using a targeted approach. Various molecular species of glycerophospholipids, glycerolipids, and sterols were significantly reduced in HαT patients. Out of a possible 1127 lipids, 521 lipid species were detected, and relative quantities were calculated. Sixty‐four lipids were significantly reduced in urinary exosomes of HαT patients compared to controls. All significantly reduced sphingolipids and most of the phospholipids were saturated or mono‐unsaturated lipids. These results suggest exosome secretion is augmented in HαT patients and the lipids within these exosomes may be involved in various biological processes. The unique lipid composition of urinary exosomes from HαT patients will contribute to our understanding of the biochemistry of this disease.

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“…The ability of adiponectin to reduce tissue ceramide levels has been posited to explain its insulin sensitizing and anti-inflammatory properties (11)(12)(13). Adiponectin also has been shown to bind a separate GPI-linked receptor T-cadherin (14), which has recently been shown to also reduce tissue ceramide levels by triggering the release of exosomes (15). These findings together suggest a role for adiponectin in ameliorating metabolic disease by altering tissue lipids, especially ceramides, via receptor binding and activation of downstream intracellular processes.…”

Section: Introductionmentioning

confidence: 99%

Adiponectin and related C1q/TNF-related proteins bind selectively to anionic phospholipids and sphingolipids

Bian

Lim

et al. 2019

Preprint

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Adiponectin (also known as Acrp30) is a well-known adipokine associated with protection from cardiovascular disease, insulin resistance, and inflammation. Though multiple studies have investigated the mechanism of action of adiponectin and its relationship with tissue ceramide levels, several aspects of adiponectin biology remain unexplained, including its high circulating levels, tendency to oligomerize, and marked structural similarity to the opsonin C1q. Given the connection between adiponectin and ceramide metabolism, and the lipid-binding properties of C1q, we hypothesized that adiponectin may function as a lipid binding protein. Indeed, we found that recombinant adiponectin bound to various anionic phospholipids and sphingolipids, including phosphatidylserine, ceramide-1-phosphate, and sulfatide. The globular head-domain of adiponectin was necessary and sufficient for lipid binding. Adiponectin oligomerization was also observed to be critical for efficient lipid binding. In addition to lipids in liposomes, adiponectin bound LDL in an oligomerization-dependent manner. Other C1qTNF-related protein (CTRP) family members Cbln1, CTRP1, CTRP5, and CTRP13 also bound similar target lipids in 2 liposomes. These findings suggest that adiponectin and other CTRP family members may not only function as classical hormones, but also as lipid binding opsonins or carrier proteins.

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

Cited by 145 publications

References 74 publications

Exosomes: Revisiting their role as “garbage bags”

Exosomes: Revisiting their role as “garbage bags”

Lipidomic analysis of urinary exosomes from hereditary α‐tryptasemia patients and healthy volunteers

Adiponectin and related C1q/TNF-related proteins bind selectively to anionic phospholipids and sphingolipids

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