Adipose Tissue Exosome-Like Vesicles Mediate Activation of Macrophage-Induced Insulin Resistance

Deng, Zhongbin; Poliakov, Anton; Hardy, Robert W.; Clements, Ronald H.; Liu, Cunren; Liu, Yuelong; Wang, Jianhua; Xiang, Xiaoyu; Zhang, Shuangqin; Zhuang, Xiaoying; Shah, Spandan V.; Sun, Dongmei; Michalek, Sue; Grizzle, William E.; Garvey, Timothy; Mobley, Jim; Zhang, Huang‐Ge

doi:10.2337/db09-0216

Cited by 452 publications

(466 citation statements)

References 48 publications

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“…These results suggest that exosomes derived from obese mice promote activation of macrophages. Previously, Deng et al (2009) reported that injection of exosomes isolated from culture supernatant of visceral adipose tissues excited from ob/ob mice led to increase in IL-6 and TNF-α levels and induce insulin resistance in recipient mice (Deng et al, 2009) In conclusion, the present study showed that serum adiponectin is partially associated with exosomes in mice. Considering that adiponectin is produced exclusively by adipocytes, adiponectin associated exosomes in serum could be derived from adipocytes.…”

Section: Resultssupporting

confidence: 58%

“…In fact, previous in vitro studies have demonstrated that mouse exosomes are associated with adiponectin. Deng et al and Sano et al respectively identified adiponectin by proteomic analysis in the exosomes released from cultured mouse adipose tissue and mouse adipocyte cell line 3T3-L1 (Deng et al, 2009;Sano et al, 2014). Given that adiponectin is produced exclusively by adipocytes, and considering that cultured adipose tissue and 3T3-L1 adipocytes release exosomes (Deng et al, 2009;Sano et al, 2014), it is possible that adiponectin-associated exosomes in serum are derived from adipocytes.…”

Section: Resultsmentioning

confidence: 99%

“…Similarly, this study observed that the protein concentration in the exosome fraction was higher in ob/ob mice than in +/+ mice, although there were no differences between HFD-fed obese and NFD-fed lean mice. In addition, cultured adipose tissue of ob/ob mice and diet-induced obese mice released more exosomal proteins than wild-type lean mice (Deng et al, 2009). Thus, it appears likely that obesity increases the release of exosomal proteins from adipose tissue, although the mechanism behind this release and the physiological implications remain unknown.…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies have identified exosomes in the culture supernatant of mouse adipose tissues (Deng et al, 2009), rat primary adipocytes (Müller et al, 2009a;Müller et al, 2009b;Müller et al, 2011), and mouse adipocyte cell line 3T3-L1 (Ogawa et al, 2010;Sano et al, 2014). Deng et al (2009) to lipogenesis and promote lipid accumulation in recipient 3T3-L1 adipocytes (Sano et al, 2014).…”

Section: Aim Of Studymentioning

confidence: 99%

“…Apart from biological fluids which are represented in vivo study, in vitro study of exosomes released in conditioned media from many cell types helps us to understand further the physiological function of exosomes. Importantly, to avoid the contamination of exosomes from serum used in the cell culture media, the serum must be eliminated exosomes by ultracentrifugation at 100,000xg overnight before using in the experiment (Deng et al, 2009;Sun et al, 2010;Van Niel, 2006;Vlassov et al, 2012).…”

Section: A) B)mentioning

confidence: 99%

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Adiponectin is partially associated with exosomes in mouse serum

Phoonsawat

Aoki-Yoshida

Tsuruta

et al. 2014

Biochemical and Biophysical Research Communications

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Previous studies suggest that adipocyte-derived exosomes play a role in cell-to-cell communication during the development of metabolic diseases. However, the characteristics and function of exosomes released from adipocytes in vivo remain to be elucidated. Clearly, exosomes released from adipocytes could exist in the circulation. In addition, because the composition of exosomes is heterogenic, depending on the cellular origin of the exosome, adipocyte-derived exosomes could be accompanied by molecules produced specifically in adipocytes. In this context, this study postulated that such molecules associated with exosomes in the serum could be markers for adipocyte-derived exosomes in vivo. This study particularly focused on secretory proteins produced specifically in adipocytes, namely adipocytokines including adiponectin, leptin, and resistin. Serum adiponectin is partially associated with exosomesBased on western blotting, CD63, a well-known protein marker of exosomes, was concentrated in the pellet of mouse serum after ultracentrifugation, suggesting successful isolation of exosomes. Western blotting detected adiponectin but no leptin and only trace amounts of resistin in the exosome fraction. After ultracentrifugation on a discontinuous gradient, both adiponectin and CD63 were detected in a fraction at a density of 1.17 g/mL, consistent with the density of exosomes. The adiponectin signal in the exosome fraction was decreased by proteinase K treatment and completely quenched by a combination of proteinase K and Triton X-100. These results suggest that a portion of adiponectin exists as a transmembrane protein in the exosomes in mouse serum. showed that the concentration of adiponectin in the serum and the ratio of adiponectin to total protein in the exosome fraction were lower in obese mice than in lean mice.In conclusion, this study showed that serum adiponectin is partially associated with exosomes in mice. Considering that adiponectin is produced exclusively by adipocytes, adiponectin-associated exosomes in serum could be derived from adipocytes. This study proposes that adiponectin could be a marker for exosomes released from adipocytes in vivo.iii

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Section: Resultssupporting

confidence: 58%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Aim Of Studymentioning

confidence: 99%

Section: A) B)mentioning

confidence: 99%

See 3 more Smart Citations

Adiponectin is partially associated with exosomes in mouse serum

Phoonsawat

Aoki-Yoshida

Tsuruta

et al. 2014

Biochemical and Biophysical Research Communications

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Immunometabolism of human autoimmune diseases: from metabolites to extracellular vesicles

et al. 2017

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Edited by Wilfried EllmeierImmunometabolism focuses on the mechanisms regulating the impact of metabolism on lymphocyte activity and autoimmunity outbreak. The adipose tissue is long known to release adipokines, either pro-or anti-inflammatory factors bridging nutrition and immune function. More recently, adipocytes were discovered to also release extracellular vesicles (EVs) containing a plethora of biological molecules, including metabolites and microRNAs, which can regulate cell function/metabolism in distant tissues, suggesting that immune regulatory function by the adipose tissue may be far more complex than originally thought. Moreover, EVs were also identified as important mediators of immune cell-to-cell communication, adding a further microenvironmental mechanism of plasticity to fine-tune specific lymphocyte responses. This Review will first focus on the known mechanisms by which metabolism impacts immune function, presenting a systemic (nutrition and long-ranged adipokines) and a cellular point of view (metabolic pathway derangement in autoimmunity). It will then discuss the new discoveries concerning how EVs may act as nanometric vehicles integrating immune/metabolic responses at the level of the extracellular environment and affecting pathological processes.Keywords: adipose tissue; autoimmunity; extracellular microRNAs; extracellular vesicles; lymphocytes Immunometabolism is the research field that links immunology and metabolism, originally regarded as distinct disciplines [1]. Growing interest in the field has being fostered by recent understanding that the metabolic state of an organism has an impact on lymphocyte physiology and activity. CD4

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Comparison of separation methods for tissue‐derived extracellular vesicles in the liver, heart, and skeletal muscle

et al. 2021

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Extracellular vesicles (EVs), which are nanosized vesicles released by cells as intracellular messengers, have high potential as biomarkers. EVs are usually collected from in vitro sources, such as cell culture media or biofluids, and not from tissues. Techniques enabling direct collection of EVs from tissues will extend the applications of EVs. We compared methods for separating EVs from solid liver, heart, and skeletal muscle. Compared with a precipitation method, an ultracentrifugation‐based method for collection of EVs from solid tissues yielded a higher proportion of EVs positive for EV‐related markers, with minimum levels of intracellular organelle‐related markers. Some tissue‐specific modifications, such as a sucrose cushion step, may improve the yield and purity of the collected EVs.

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Adipose Tissue Exosome-Like Vesicles Mediate Activation of Macrophage-Induced Insulin Resistance

Cited by 452 publications

References 48 publications

Adiponectin is partially associated with exosomes in mouse serum

Adiponectin is partially associated with exosomes in mouse serum

Immunometabolism of human autoimmune diseases: from metabolites to extracellular vesicles

Comparison of separation methods for tissue‐derived extracellular vesicles in the liver, heart, and skeletal muscle

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