Adipocyte-derived microvesicles contain RNA that is transported into macrophages and might be secreted into blood circulation

Ogawa, Rumiko; Tanaka, Chie; Nagasaki, Haruka; Sugimura, Kazuto; Okumura, Katsuhiko; Nakagawa, Yoshimi; Aoki, Naohito

doi:10.1016/j.bbrc.2010.07.008

Cited by 140 publications

(118 citation statements)

References 26 publications

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“…Thus, secreted miRNAs can serve as a novel class of signaling molecules in mediating intercellular communication [15]. The novel and important functions of the secreted miRNAs were also reported by many other groups [18][19][20][21]. The identification of circulating miRNAs, mainly delivered by cell-secreted MVs, as stable and active signaling molecules opens a new field of research in intercellular and interorganelle signal transduction.…”

Section: Introductionmentioning

confidence: 72%

Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA

et al. 2011

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Our previous studies have demonstrated that stable microRNAs (miRNAs) in mammalian serum and plasma are actively secreted from tissues and cells and can serve as a novel class of biomarkers for diseases, and act as signaling molecules in intercellular communication. Here, we report the surprising finding that exogenous plant miRNAs are present in the sera and tissues of various animals and that these exogenous plant miRNAs are primarily acquired orally, through food intake. MIR168a is abundant in rice and is one of the most highly enriched exogenous plant miRNAs in the sera of Chinese subjects. Functional studies in vitro and in vivo demonstrated that MIR168a could bind to the human/mouse low-density lipoprotein receptor adapter protein 1 (LDLRAP1) mRNA, inhibit LDLRAP1 expression in liver, and consequently decrease LDL removal from mouse plasma. These findings demonstrate that exogenous plant miRNAs in food can regulate the expression of target genes in mammals.

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Section: Introductionmentioning

confidence: 72%

Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA

et al. 2011

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“…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%

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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“…Indeed, mammalian cells in culture have been reported to export miRNAs into the extracellular environment (13 ), and some circulating miRNAs have been revealed as useful biomarkers for human diseases. Although circulating miRNAs seem to be involved in intercellular communication (14 ), it remains unclear how extracellular miRNAs are associated with cellular components (15 ), and the main function of circulating miRNAs remains elusive.…”

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confidence: 99%

Targeting the Circulating MicroRNA Signature of Obesity

et al. 2013

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BACKGROUND Genomic studies have yielded important insights into the pathogenesis of obesity. Circulating microRNAs (miRNAs) are valuable biomarkers of systemic diseases and potential therapeutic targets. We sought to define the circulating pattern of miRNAs in obesity and examine changes after weight loss. METHODS We assessed the genomewide circulating miRNA profile cross-sectionally in 32 men and after surgery-induced weight loss in 6 morbidly obese patients. The most relevant miRNAs were cross-sectionally validated in 80 men and longitudinally in 22 patients (after surgery-induced weight loss). We evaluated the effects of diet-induced weight loss in 9 obese patients. Thirty-six circulating miRNAs were associated with anthropometric variables in the initial sample. RESULTS In the validation study, morbidly obese patients showed a marked increase of miR-140-5p, miR-142-3p (both P < 0.0001), and miR-222 (P = 0.0002) and decreased levels of miR-532–5p, miR-125b, miR-130b, miR-221, miR-15a, miR-423-5p, and miR-520c-3p (P < 0.0001 for all). Interestingly, in silico targets leukemia inhibitory factor receptor (LIFR) and transforming growth factor receptor (TGFR) of miR-140-5p, miR-142-3p, miR-15a, and miR-520c-3p circulated in association with their corresponding miRNAs. Moreover, a discriminant function of 3 miRNAs (miR-15a, miR-520c-3p, and miR-423-5p) was specific for morbid obesity, with an accuracy of 93.5%. Surgery-induced (but not diet-induced) weight loss led to a marked decrease of miR-140-5p, miR-122, miR-193a-5p, and miR-16-1 and upregulation of miR-221 and miR-199a-3p (P < 0.0001 for all). CONCLUSIONS Circulating miRNAs are deregulated in severe obesity. Weight loss–induced changes in this profile and the study of in silico targets support this observation and suggest a potential mechanistic relevance.

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Adipocyte-derived microvesicles contain RNA that is transported into macrophages and might be secreted into blood circulation

Cited by 140 publications

References 26 publications

Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA

Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA

Adiponectin is partially associated with exosomes in mouse serum

Targeting the Circulating MicroRNA Signature of Obesity

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