Adipocyte-Derived Microvesicles Are Associated with Multiple Angiogenic Factors and Induce Angiogenesis in Vivo and in Vitro

Aoki, Naohito; Yokoyama, Rumi; Asai, Noriyuki; Ohki, Makiko; Ohki, Yuichi; Kusubata, Kaori; Heissig, Beate; Hattori, Koichi; Nakagawa, Yoshimi; Matsuda, Tsukasa

doi:10.1210/en.2009-1023

Cited by 55 publications

(43 citation statements)

References 33 publications

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“…Many angiogenic factors could be secreted by adipocytes in vitro and in vivo (31). We consistently found that proangiogenic factors, including VEGF, FGF-2, and PlGF, were also secreted by adipocytes in vitro ( Supplementary Fig.…”

Section: The Antiangiogenic Activity Of Endostatin Contributes To Itsmentioning

confidence: 61%

Endostatin Prevents Dietary-Induced Obesity by Inhibiting Adipogenesis and Angiogenesis

Wang

Chen

et al. 2015

Diabetes

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Endostatin is a well-known angiogenesis inhibitor. Although angiogenesis has been considered as a potential therapeutic target of obesity, the inhibitory effect of endostatin on adipogenesis and dietary-induced obesity has never been demonstrated. Adipogenesis plays a critical role in controlling adipocyte cell number, body weight, and metabolic profile in a homeostatic state. Here we reveal that endostatin inhibits adipogenesis and dietary-induced obesity. The antiadipogenic mechanism of endostatin lies in its interaction with Sam68 RNA-binding protein in the nuclei of preadipocytes. This interaction competitively impairs the binding of Sam68 to intron 5 of mammalian target of rapamycin (mTOR), causing an error in mTOR transcript. This consequently decreases the expression of mTOR, results in decreased activities of the mTOR complex 1 pathway, and leads to defects in adipogenesis. Moreover, our findings demonstrate that the antiangiogenic function of endostatin also contributes to its obesity-inhibitory activity. Through the combined functions on adipogenesis and angiogenesis, endostatin prevents dietary-induced obesity and its related metabolic disorders, including insulin resistance, glucose intolerance, and hepatic steatosis. Thus, our findings reveal that endostatin has a potential application for antiobesity therapy and the prevention of obesity-related metabolic syndromes.

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Section: The Antiangiogenic Activity Of Endostatin Contributes To Itsmentioning

confidence: 61%

Endostatin Prevents Dietary-Induced Obesity by Inhibiting Adipogenesis and Angiogenesis

Wang

Chen

et al. 2015

Diabetes

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“…In addition to endothelial and other diseaserelated cells, adipocytes have been recently reported to secrete MPs (58 ). Adipocyte-derived MPs are associated with multiple angiogenic factors and play a role in angiogenesis in adipose tissue.…”

Section: Mps Alter Endothelial Cell Survival and Angiogenesismentioning

confidence: 99%

“…Adipocyte-derived MPs are associated with multiple angiogenic factors and play a role in angiogenesis in adipose tissue. Leptin, tumor necrosis factor-␣ (TNF-␣), and bFGF from adipocyte-derived MPs are involved in endothelial cell migration and tube formation (58 ).…”

Section: Mps Alter Endothelial Cell Survival and Angiogenesismentioning

confidence: 99%

Evolving Role of Microparticles in the Pathophysiology of Endothelial Dysfunction

2013

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BACKGROUND Endothelial dysfunction is an early event in the development and progression of a wide range of cardiovascular diseases. Various human studies have identified that measures of endothelial dysfunction may offer prognostic information with respect to vascular events. Microparticles (MPs) are a heterogeneous population of small membrane fragments shed from various cell types. The endothelium is one of the primary targets of circulating MPs, and MPs isolated from blood have been considered biomarkers of vascular injury and inflammation. CONTENT This review summarizes current knowledge of the potential functional role of circulating MPs in promoting endothelial dysfunction. Cells exposed to different stimuli such as shear stress, physiological agonists, proapoptotic stimulation, or damage release MPs, which contribute to endothelial dysfunction and the development of cardiovascular diseases. Numerous studies indicate that MPs may trigger endothelial dysfunction by disrupting production of nitric oxide release from vascular endothelial cells and subsequently modifying vascular tone. Circulating MPs affect both proinflammatory and proatherosclerotic processes in endothelial cells. In addition, MPs can promote coagulation and inflammation or alter angiogenesis and apoptosis in endothelial cells. SUMMARY MPs play an important role in promoting endothelial dysfunction and may prove to be true biomarkers of disease state and progression.

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“…Several integral, cytosolic and nuclear proteins such as caveolin-1, c-Src kinase, and heat shock protein 70 were also microvesicle components. Proteomic analysis of the microvesicles revealed that many other proteins, such as extracellular matrix-related proteins (11) and multiple angiogenic factors, were also present (12). The discovery of adipocyte-derived microvesicles might represent a novel component of fat cell biology that must be validated under in vivo conditions.…”

Section: Fat Cell Secretionsmentioning

confidence: 99%

Historical perspectives in fat cell biology: the fat cell as a model for the investigation of hormonal and metabolic pathways

Lafontan

2012

American Journal of Physiology-Cell Physiology

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Lafontan M. Historical perspectives in fat cell biology: the fat cell as a model for the investigation of hormonal and metabolic pathways. Am J Physiol Cell Physiol 302: C327-C359, 2012. First published September 7, 2011; doi:10.1152/ajpcell.00168.2011.-For many years, there was little interest in the biochemistry or physiology of adipose tissue. It is now well recognized that adipocytes play an important dynamic role in metabolic regulation. They are able to sense metabolic states via their ability to perceive a large number of nervous and hormonal signals. They are also able to produce hormones, called adipokines, that affect nutrient intake, metabolism and energy expenditure. The report by Rodbell in 1964 that intact fat cells can be obtained by collagenase digestion of adipose tissue revolutionized studies on the hormonal regulation and metabolism of the fat cell. In the context of the advent of systems biology in the field of cell biology, the present seems an appropriate time to look back at the global contribution of the fat cell to cell biology knowledge. This review focuses on the very early approaches that used the fat cell as a tool to discover and understand various cellular mechanisms. Attention essentially focuses on the early investigations revealing the major contribution of mature fat cells and also fat cells originating from adipose cell lines to the discovery of major events related to hormone action (hormone receptors and transduction pathways involved in hormonal signaling) and mechanisms involved in metabolite processing (hexose uptake and uptake, storage, and efflux of fatty acids). Dormant preadipocytes exist in the stroma-vascular fraction of the adipose tissue of rodents and humans; cell culture systems have proven to be valuable models for the study of the processes involved in the formation of new fat cells. Finally, more recent insights into adipocyte secretion, a completely new role with major metabolic impact, are also briefly summarized. history; adipocytes; insulin action; 3T3-L1 cells; glucose transport; fatty acids; lipolysis; catecholamines; preadipocytes SINCE THE EARLIEST TIMES, attention has been directed toward fat-related questions. It is currently accepted that the ability to store fat in adipose tissue was a major advantage for survival during cold winters and periods of food shortage for our "primitive" hunter ancestors. However, in modern societies, with increased food availability and nutritional efficacy, excessive fat deposition is frequently associated with degenerative or metabolic diseases. As early as 1901, life insurance companies noted that excess weight, particularly around the abdomen, was linked to reduced life expectancy. The risk was confirmed in the seminal studies of Vague (366) in Marseilles, who established the importance of abdominal (central) obesity in conferring excess mortality. The health hazard of obesity is not considered in the present review, which, rather, focuses on adipose tissue and adipocytes.

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Adipocyte-Derived Microvesicles Are Associated with Multiple Angiogenic Factors and Induce Angiogenesis in Vivo and in Vitro

Cited by 55 publications

References 33 publications

Endostatin Prevents Dietary-Induced Obesity by Inhibiting Adipogenesis and Angiogenesis

Endostatin Prevents Dietary-Induced Obesity by Inhibiting Adipogenesis and Angiogenesis

Evolving Role of Microparticles in the Pathophysiology of Endothelial Dysfunction

Historical perspectives in fat cell biology: the fat cell as a model for the investigation of hormonal and metabolic pathways

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