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


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.

SUBMITTER: Hubal MJ 

PROVIDER: S-EPMC5182153 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Hubal Monica J MJ   Nadler Evan P EP   Ferrante Sarah C SC   Barberio Matthew D MD   Suh Jung-Hyuk JH   Wang Justin J   Dohm G Lynis GL   Pories Walter J WJ   Mietus-Snyder Michelle M   Freishtat Robert J RJ  

Obesity (Silver Spring, Md.) 20161124 1


<h4>Objective</h4>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.<h4>Methods</h4>African American female subjects w  ...[more]

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