title: Circulating adipocyte-derived exosomal MicroRNAs associated with decreased insulin resistance after gastric bypass.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  These data indicate that circulating adipocyte-derived exosomes are modified following gastric bypass surgery and correlate to improved postsurgery insulin resistance.
authors.affiliation: Department of Integrative Systems Biology, George Washington University, Washington, DC, USA.|Department of Exercise and Nutrition Sciences, George Washington University, Washington, DC, USA.
authors.forename: Monica J
authors.initials: MJ
authors.lastname: Hubal
authors.affiliation: Department of Integrative Systems Biology, George Washington University, Washington, DC, USA.|Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Medical Center, Washington, DC, USA.|Division of Pediatric Surgery, Children's National Medical Center, Washington, DC, USA.
authors.forename: Evan P
authors.initials: EP
authors.lastname: Nadler
authors.affiliation: Department of Integrative Systems Biology, George Washington University, Washington, DC, USA.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Ferrante
authors.affiliation: Department of Integrative Systems Biology, George Washington University, Washington, DC, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Barberio
authors.affiliation: Center for Nutrition and Metabolism, Children's Hospital Oakland Research Institute, Oakland, California, USA.
authors.forename: Jung-Hyuk
authors.initials: JH
authors.lastname: Suh
authors.affiliation: Department of Integrative Systems Biology, George Washington University, Washington, DC, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Physiology, East Carolina University, Greenville, North Carolina, USA.
authors.forename: G Lynis
authors.initials: GL
authors.lastname: Dohm
authors.affiliation: Department of Surgery, East Carolina University, Greenville, North Carolina, USA.
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Pories
authors.affiliation: Department of Pediatrics, Children's National Medical Center, Washington, DC, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Mietus-Snyder
authors.affiliation: Department of Integrative Systems Biology, George Washington University, Washington, DC, USA.|Department of Pediatrics, Children's National Medical Center, Washington, DC, USA.|Division of Emergency Medicine, Children's National Medical Center, Washington, DC, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Freishtat
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000328:Adult; D001741:Black or African American; D000597:Amino Acids, Branched-Chain / Q000378:metabolism; D005260:Female; D015390:Gastric Bypass; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D035683:MicroRNAs / Q000032:analysis*; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*
chemical_list: D000597:Amino Acids, Branched-Chain; D007328:Insulin; D035683:MicroRNAs