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3. MOESM2 of Cholesterol efflux alterations in adolescent obesity: role of adipose-derived extracellular vesical microRNAs

Author

Barberio, Matthew, Kasselman, Lora, Playford, Martin, Epstein, Samuel, Renna, Heather, Goldberg, Madeleine, DeLeon, Joshua, Voloshyna, Iryna, Barlev, Ashley, Salama, Michael, Ferrante, Sarah, Nadler, Evan, Mehta, Nehal, Reiss, Allison, and Freishtat, Robert

Abstract

Additional file 2: Table S1. Mature Cholesterol Efflux MicroRNA for Multivariate Analysis. Table S2. K-Means Cluster Statistics.

Published
2019
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8. Circulating adipocyte-derived exosomal MicroRNAs associated with decreased insulin resistance after gastric bypass.

Author

Hubal, Monica J., Nadler, Evan P., Ferrante, Sarah C., Barberio, Matthew D., Suh, Jung‐Hyuk, Wang, Justin, Dohm, G. Lynis, Pories, Walter J., Mietus‐Snyder, Michelle, and Freishtat, Robert J.

Subjects
MICRORNA genetics, INSULIN resistance, GASTRIC bypass, OBESITY genetics, FAT cells, EXOSOMES, PREVENTION, RNA analysis, BLACK people, BRANCHED chain amino acids, GENES, INSULIN, OBESITY, RESEARCH funding
Abstract

Objective: Exosomes from obese adipose contain dysregulated microRNAs linked to insulin signaling, as compared with lean controls, providing a direct connection between adiposity and insulin resistance. This 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 1 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 postsurgery, patients showed decreased BMI (-18.6 ± 5.1 kg/m2 ; P < 0.001), ameliorated insulin resistance (HOMA: 1.94 ± 0.6 presurgery, 0.49 ± 0.1 postsurgery; P < 0.001), and altered metabolites including branched chain amino acids (BCAA). Biological pathway 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 the data set. 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 postsurgery insulin resistance. [ABSTRACT FROM AUTHOR]

Published
2017
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10. Adipocyte-derived exosomal miRNAs: a novel mechanism for obesity-related disease

Author

Ferrante, Sarah C., Nadler, Evan P., Pillai, Dinesh K., Hubal, Monica J., Wang, Zuyi, Wang, Justin M., Gordish-Dressman, Heather, Koeck, Emily, Sevilla, Samantha, Wiles, Andrew A., and Freishtat, Robert J.

Abstract

Background:Obesity is frequently complicated by comorbid conditions, yet how excess adipose contributes is poorly understood. Although adipocytes in obese individuals induce systemic inflammation via secreted cytokines, another potential mediator has recently been identified (i.e., adipocyte-derived exosomes). We hypothesized that adipocyte-derived exosomes contain mediators capable of activating end-organ inflammatory and fibrotic signaling pathways.Methods:We developed techniques to quantify and characterize exosomes shed by adipocytes from seven obese (age: 12–17.5 y, BMI: 33–50?kg/m2) and five lean (age: 11–19 y, BMI: 22–25?kg/m2) subjects.Results:Abundant exosomal miRNAs, but no mRNAs, were detected. Comparison of obese vs. lean visceral adipose donors detected 55 differentially expressed miRNAs (P < 0.05; fold change =|1.2|). qRT-PCR confirmed downregulation of miR-148b (ratio = 0.2 (95% confidence interval = 0.1, 0.6)) and miR-4269 (0.3 (0.1, 0.8)), and upregulation of miR-23b (6.2 (2.2, 17.8)) and miR-4429 (3.8 (1.1-13.4)). Pathways analysis identified TGF-ß signaling and Wnt/ß-catenin signaling among the top canonical pathways expected to be altered with visceral adiposity based on projected mRNA targets for the 55 differentially expressed miRNAs. A select mRNA target was validated in vitro.Conclusion:These data show that visceral adipocytes shed exosomal-mediators predicted to regulate key end-organ inflammatory and fibrotic signaling pathways.

Published
2015
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