Current understanding of the role of Adipose-derived Extracellular Vesicles in Metabolic Homeostasis and Diseases: Communication from the distance between cells/tissues

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Abstract

Extracellular vesicles (EVs) including exosomes, microvesicles (MVs), and apoptotic bodies, are small membrane vesicular structures that are released during cell activation, senescence, or programmed cell death, including apoptosis, necroptosis, and pyroptosis. EVs serve as novel mediators for long-distance cell-to-cell communications and can transfer various bioactive molecules, such as encapsulated cytokines and genetic information from their parental cells to distant target cells. In the context of obesity, adipocyte-derived EVs are implicated in metabolic homeostasis serving as novel adipokines. In particular, EVs released from brown adipose tissue or adipose-derived stem cells may help control the remolding of white adipose tissue towards browning and maintaining metabolic homeostasis. Interestingly, EVs may even serve as mediators for the transmission of metabolic dysfunction across generations. Also, EVs have been recognized as novel modulators in various metabolic disorders, including insulin resistance, diabetes mellitus, and non-alcoholic fatty liver disease. In this review, we summarize the latest progress from basic and translational studies regarding the novel effects of EVs on metabolic diseases. We also discuss EV-mediated cross-talk between adipose tissue and other organs/tissues that are relevant to obesity and metabolic diseases, as well as the relevant mechanisms, providing insight into the development of new therapeutic strategies in obesity and metabolic diseases.

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Most cited references 92

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Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder.

Q. Chen, M. Yan, Z. Cao … (2016)

Increasing evidence indicates that metabolic disorders in offspring can result from the father's diet, but the mechanism remains unclear. In a paternal mouse model given a high-fat diet (HFD), we showed that a subset of sperm transfer RNA-derived small RNAs (tsRNAs), mainly from 5' transfer RNA halves and ranging in size from 30 to 34 nucleotides, exhibited changes in expression profiles and RNA modifications. Injection of sperm tsRNA fractions from HFD males into normal zygotes generated metabolic disorders in the F1 offspring and altered gene expression of metabolic pathways in early embryos and islets of F1 offspring, which was unrelated to DNA methylation at CpG-enriched regions. Hence, sperm tsRNAs represent a paternal epigenetic factor that may mediate intergenerational inheritance of diet-induced metabolic disorders.

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Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes

K. Teng, M Adam Mahmood, C Wu … (1985)

Using ferritin-labeled protein A and colloidal gold-labeled anti-rabbit IgG, the fate of the sheep transferrin receptor has been followed microscopically during reticulocyte maturation in vitro. After a few minutes of incubation at 37 degrees C, the receptor is found on the cell surface or in simple vesicles of 100-200 nm, in which the receptor appears to line the limiting membrane of the vesicles. With time (60 min or longer), large multivesicular elements (MVEs) appear whose diameter may reach 1-1.5 micron. Inside these large MVEs are round bodies of approximately 50-nm diam that bear the receptor at their external surfaces. The limiting membrane of the large MVEs is relatively free from receptor. When the large MVEs fuse with the plasma membrane, their contents, the 50-nm bodies, are released into the medium. The 50-nm bodies appear to arise by budding from the limiting membrane of the intracellular vesicles. Removal of surface receptor with pronase does not prevent exocytosis of internalized receptor. It is proposed that the exocytosis of the approximately 50-nm bodies represents the mechanism by which the transferrin receptor is shed during reticulocyte maturation.

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Caspases in Cell Death, Inflammation, and Disease

Nina Van Opdenbosch, Mohamed Lamkanfi (2019)

Caspases are an evolutionary conserved family of cysteine proteases that are centrally involved in cell death and inflammation responses. A wealth of foundational insight into the molecular mechanisms that control caspase activation has emerged in recent years. Important advancements include the identification of additional inflammasome platforms and pathways that regulate activation of inflammatory caspases; the discovery of gasdermin D as the effector of pyroptosis and interleukin (IL)-1 and IL-18 secretion; and the existence of substantial crosstalk between inflammatory and apoptotic initiator caspases. A better understanding of the mechanisms regulating caspase activation has supported initial efforts to modulate dysfunctional cell death and inflammation pathways in a suite of communicable, inflammatory, malignant, metabolic and neurodegenerative diseases. Here, we review current understanding of caspase biology with a prime focus on the inflammatory caspases, and outline important topics for future experimentation.

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Author and article information

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Journal ID (nlm-ta): Theranostics

Journal ID (iso-abbrev): Theranostics

Journal ID (publisher-id): thno

Title: Theranostics

Publisher: Ivyspring International Publisher (Sydney )

ISSN (Electronic): 1838-7640

Publication date Collection: 2020

Publication date (Electronic): 12 June 2020

Volume: 10

Issue: 16

Pages: 7422-7435

Affiliations

[1 ]Department of Endocrinology, Health Management Center, Tianjin Union Medical Center, Nankai University Affiliated Hospital, Tianjin, 300121, P.R. China.

[2 ]Department of Dermatology, Perelman School of Medicine, University of Pennsylvania.

[3 ]Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA 19104, USA.

[4 ]Shanghai National Research Centre for Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Author notes

✉ Corresponding authors: E-mails: linjingna@ 123456umc.net.cn (Jing-Na Lin); li_chunjun@ 123456126.com (Chun-Jun Li); lium1@ 123456pennmedicine.upenn.edu (Ming-Lin Liu).

#These authors contributed equally to this review.

Competing Interests: The authors have declared that no competing interest exists.

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Publisher ID: thnov10p7422

DOI: 10.7150/thno.42167

PMC ID: 7330853

PubMed ID: 32642003

SO-VID: eea29d70-8520-4a20-8aef-eafbec6108a2

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This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

Current understanding of the role of Adipose-derived Extracellular Vesicles in Metabolic Homeostasis and Diseases: Communication from the distance between cells/tissues

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Most cited references 92

Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder.

Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes

Caspases in Cell Death, Inflammation, and Disease

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