title: Arterial insulin resistance in Yucatan micropigs with diet-induced obesity and metabolic syndrome.
abstract: OBJECTIVE
  Metabolic syndrome affects a large proportion of the population and increases cardiovascular disease risk. Because metabolic syndrome often co-exists clinically with atherosclerosis, it is difficult to distinguish the respective contributions of the components to vascular abnormalities. Accordingly, we utilized a porcine dietary model of metabolic syndrome without atherosclerosis to investigate early abnormalities of vascular function and signaling.
  
  
  METHODS
  Thirty-two Yucatan micropigs were fed either a high-fat, high-simple-sugar, high-calorie (HFHS) or standard chow diet (STD) for 6 months. Neither diet contained added cholesterol. Blood pressure and flow-mediated vasodilatation were assessed at baseline and 6 months. Aortas were harvested at 6 months to assess histology, insulin signaling, and endothelial nitric oxide (eNOS) phosphorylation.
  
  
  RESULTS
  HFHS pigs developed characteristics of metabolic syndrome including obesity, dyslipidemia, and insulin resistance, but without histologic evidence of atherosclerosis. Although arterial intima-media thickness did not differ between groups, vascular dysfunction in HFHS was manifest by increased blood pressure and impaired flow-mediated vasodilation of the femoral artery. Compared with STD, aortas from HFHS exhibited increased p85α expression and Ser307 IRS-1 phosphorylation, and blunted insulin-stimulated IRS-1-associated phosphatidylinositol (PI) 3-kinase activity. In the absence of insulin stimulation, aortic Akt Ser473-phosphorylation was greater in HFHS than in STD. With insulin stimulation, Akt phosphorylation increased in STD, but not HFHS. Insulin-induced Ser1177-phosphorylation of eNOS was decreased in HFHS, compared with STD.
  
  
  CONCLUSIONS
  Pigs with metabolic syndrome develop early vascular dysfunction and aortic insulin signaling abnormalities, and could be a useful model for early human vascular abnormalities in this condition.
authors.affiliation: Endocrine Section, VA Medical Center, Denver, and University of Colorado Anschutz Medical Campus/School of Medicine, Aurora, CO, USA. Cecilia.Wang@UCDenver.edu
authors.forename: Cecilia C
authors.initials: CC
authors.lastname: Low Wang
authors.forename: Li
authors.initials: L
authors.lastname: Lu
authors.forename: J Wayne
authors.initials: JW
authors.lastname: Leitner
authors.forename: Mohammad
authors.initials: M
authors.lastname: Sarraf
authors.forename: Roberto
authors.initials: R
authors.lastname: Gianani
authors.forename: Boris
authors.initials: B
authors.lastname: Draznin
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Greyson
authors.forename: Jane E B
authors.initials: JE
authors.lastname: Reusch
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D001158:Arteries / Q000378:metabolism; D004032:Diet; D004195:Disease Models, Animal; D005260:Female; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications* / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009765:Obesity / Q000150:complications* / Q000209:etiology / Q000378:metabolism*; D010766:Phosphorylation; D013552:Swine; D013556:Swine, Miniature; D014664:Vasodilation
chemical_list: D055504:Insulin Receptor Substrate Proteins; D052250:Nitric Oxide Synthase Type III
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