Ontology highlight
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
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]