Adipocyte Exosomes Induce Transforming Growth Factor Beta Pathway Dysregulation in Hepatocytes: A Novel Paradigm for Obesity-Related Liver Disease

Koeck, Emily S.; Sevilla, Samantha; Qureshi, Faisal; Hubal, Monica J.; Nadler, Evan P.

doi:10.1016/j.jss.2013.11.500

Cited by 11 publications

(13 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Many of these microRNAs also significantly correlate with robust clinical improvements in insulin resistance. This is consistent with our previous work, wherein we reported obesity-dysregulated microRNAs in visceral adipocyte-derived exosomes are predicted to impair insulin receptor signaling in adolescents with obesity, suggesting that obesity-dysregulated exosome signaling from adipose could be positively impacted by weight loss following bariatric surgery (15,16).…”

Section: Discussionsupporting

confidence: 93%

“…We recently described obesity-related differences in the microRNA content of exosomes derived from human obese visceral adipose tissue as compared with those from lean subjects (15) and identified adipocyte-derived exosomal signaling as a mediator linking adiposity and insulin resistance in peripheral tissues (15,16). While these previous experiments showed the chronic effects of obesity on adipocyte-derived exosomal microRNA contents, the ability of significant weight loss to reverse these changes and the potential for cardiometabolic health gains are yet to be determined.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Circulating adipocyte‐derived exosomal MicroRNAs associated with decreased insulin resistance after gastric bypass

Hubal

Nadler

Ferrante

et al. 2016

Obesity

156

148

View full text Add to dashboard Cite

Objective Exosomes from obese adipose contain dysregulated microRNAs linked to insulin signaling, as compared to lean controls, providing a direct connection between adiposity and insulin resistance. The current study tested the hypotheses that gastric bypass surgery and its subsequent weight loss would normalize adipocyte-derived-exosomal microRNAs associated with insulin signaling and the associated metabolome related to glucose homeostasis. Methods African-American female subjects with obesity (N=6; age: 38.5±6.8 years; BMI: 51.2±8.8 kg/m2) were tested before and one year after surgery. Insulin resistance (HOMA), serum metabolomics and global microRNA profiles of circulating adipocyte-derived exosomes were evaluated via ANCOVA and correlational analyses. Results One-year post-surgery, patients showed decreased BMI (−18.6±5.1 kg/m2; p<0.001), ameliorated insulin resistance (HOMA: 1.94±0.6 pre-surgery, 0.49±0.1 post-surgery; p<0.001), and altered metabolites including branched chain amino acids. Biological pathways analysis of predicted mRNA targets of 168 surgery-responsive microRNAs (p<0.05) identified the insulin signaling pathway (p=1.27E-10; 52/138 elements), among others, in our dataset. The insulin signaling pathway was also a target of 10 microRNAs correlated to changes in HOMA (p<0.05; r>0.4), and 48 microRNAs correlated to changes in BCAA levels. Conclusions These data indicate that circulating adipocyte-derived exosomes are modified following gastric bypass surgery and correlate to improved post-surgery insulin resistance.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Circulating adipocyte‐derived exosomal MicroRNAs associated with decreased insulin resistance after gastric bypass

Hubal

Nadler

Ferrante

et al. 2016

Obesity

156

148

View full text Add to dashboard Cite

show abstract

“…Exosomes from visceral fat of obese individuals may affect the development of nonalcoholic fatty liver disease. 38 miRNA profiles of VATderived exosomes from obese and lean individuals are different. 39 Presumably, obesity may cause dysregulation in the assembly of adipose-exosome biological components, resulting in the unregulated sorting of certain contents into exosomes.…”

Section: Discussionmentioning

confidence: 99%

Adipose‐Derived Exosomes Exert Proatherogenic Effects by Regulating Macrophage Foam Cell Formation and Polarization

Xie

Wang

Liu

et al. 2018

JAHA

146

View full text Add to dashboard Cite

BackgroundObesity is causally associated with atherosclerosis, and adipose tissue (AT)–derived exosomes may be implicated in the metabolic complications of obesity. However, the precise role of AT‐exosomes in atherogenesis remains unclear. We herein aimed to assess the effect of AT‐exosomes on macrophage foam cell formation and polarization and subsequent atherosclerosis development.Methods and ResultsFour types of exosomes isolated from the supernatants of ex vivo subcutaneous AT and visceral AT (VAT) explants that were derived from wild‐type mice and high‐fat diet (HFD)–induced obese mice were effectively taken up by RAW264.7 macrophages. Both treatment with wild‐type VAT exosomes and HFD‐VAT exosomes, but not subcutaneous AT exosomes, markedly facilitated macrophage foam cell generation through the downregulation of ATP‐binding cassette transporter (ABCA1 and ABCG1)–mediated cholesterol efflux. Decreased expression of liver X receptor‐α was also observed. Among the 4 types of exosomes, only HFD‐VAT exosomes significantly induced M1 phenotype transition and proinflammatory cytokine (tumor necrosis factor α and interleukin 6) secretion in RAW264.7 macrophages, which was accompanied by increased phosphorylation of NF‐κB‐p65 but not the cellular expression of NF‐κB‐p65 or IκB‐α. Furthermore, systematic intravenous injection of HFD‐VAT exosomes profoundly exacerbated atherosclerosis in hyperlipidemic apolipoprotein E–deficient mice, as indicated by the M1 marker (CD16/32 and inducible nitric oxide synthase)–positive areas and the Oil Red O/Sudan IV–stained area, without affecting the plasma lipid profile and body weight.ConclusionsThis study demonstrated a proatherosclerotic role for HFD‐VAT exosomes, which is exerted by regulating macrophage foam cell formation and polarization, indicating a novel link between AT and atherosclerosis in the context of obesity.

show abstract

“…In vitro, existence of exosomes has been reported in culture medium of adipose tissues (63), adipocytes (64,65) and ADSCs (20). Katsuda et al, by nanoparticle tracking analysis, found that ADSC-derived exosomes had peak size distribution of 150-200 nm which was larger than previously reported (28).…”

Section: Adipose Tissue Exosomesmentioning

confidence: 94%

“…2c). The TGF-b pathway has been the predicted target of these different miRNAs (65). Adipocyte exosomes activated the TGF-b pathway and increased expression of proteins which inhibit extracellular matrix degradation, such as TIMP-1, MMP-7 and PAI-1 (109,110).…”

Section: Obesitymentioning

confidence: 99%

Physiological and pathological impact of exosomes of adipose tissue

2016

View full text Add to dashboard Cite

Exosomes are nanovesicles that have emerged as a new intercellular communication system for transporting proteins and RNAs; recent studies have shown that they play a role in many physiological and pathological processes such as immune regulation, cell differentiation, infection and cancer. By transferring proteins, mRNAs and microRNAs, exosomes act as information vehicles that alter the behavior of recipient cells. Compared to direct cell-cell contact or secreted factors, exosomes can affect recipient cells in more efficient ways. In whole adipose tissues, it has been shown that exosomes exist in supernatants of adipocytes and adipose stromal cells (ADSCs). Adipocyte exosomes are linked to lipid metabolism and obesity-related insulin resistance and exosomes secreted by ADSCs are involved in angiogenesis, immunomodulation and tumor development. This review introduces characteristics of exosomes in adipose tissue, summarizes their functions in different physiological and pathological processes and provides the further insight into potential application of exosomes to disease diagnosis and treatment.

show abstract

Adipocyte Exosomes Induce Transforming Growth Factor Beta Pathway Dysregulation in Hepatocytes: A Novel Paradigm for Obesity-Related Liver Disease

Cited by 11 publications

References 0 publications

Circulating adipocyte‐derived exosomal MicroRNAs associated with decreased insulin resistance after gastric bypass

Circulating adipocyte‐derived exosomal MicroRNAs associated with decreased insulin resistance after gastric bypass

Adipose‐Derived Exosomes Exert Proatherogenic Effects by Regulating Macrophage Foam Cell Formation and Polarization

Physiological and pathological impact of exosomes of adipose tissue

Contact Info

Product

Resources

About