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- Title
Circulating adipocyte-derived exosomal MicroRNAs associated with decreased insulin resistance after gastric bypass.
- Authors
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; Freishtat, Robert J.
- Abstract
<bold>Objective: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>These data indicate that circulating adipocyte-derived exosomes are modified following gastric bypass surgery and correlate to improved postsurgery insulin resistance.
- 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
- Publication
Obesity (19307381), 2017, Vol 25, Issue 1, p102
- ISSN
1930-7381
- Publication type
journal article
- DOI
10.1002/oby.21709