title: Increased nitric oxide availability attenuates high fat diet metabolic alterations and gene expression associated with insulin resistance.
abstract: BACKGROUND
  High fat diet impairs nitric oxide (NO) bioavailability, and induces insulin resistance. The link between NO availability and the metabolic adaptation to a high fat diet is not well characterized. The purpose of this study was to investigate the effect of high fat diet on metabolism in mice with decreased (eNOS-/-) and increased (DDAH overexpressed) NO bioavailability.
  
  
  METHODS
  eNOS-/- (n = 16), DDAH (n = 24), and WT (n = 19) mice were fed a high fat diet (HFD) for 13 weeks. Body weight, biochemical parameters, adipokines and insulin were monitored. The matrigel in vivo model with CD31 immunostaining was used to assess angiogenesis. Gene expression in adipose tissues was analyzed by microarray and Real Time PCR. Comparisons of the mean values were made using the unpaired Student t test and p < 0.05 were considered statistically significant.
  
  
  RESULTS
  eNOS-/- mice gained less weight than control WT and DDAH mice. In DDAH mice, a greater increase in serum adiponectin and a lesser increment in glucose level was observed. Fasting insulin and cholesterol levels remained unchanged. The angiogenic response was increased in DDAH mice. In adipose tissue of DDAH mice, genes characteristic of differentiated adipocytes were down-regulated, whereas in eNOS-/- mice, genes associated with adipogenesis, fatty acid and triglyceride synthesis were upregulated.
  
  
  CONCLUSIONS
  Our results indicate that increased NO availability attenuates some HFD induced alterations in metabolism and gene expression associated with insulin resistance.
authors.affiliation: Department of Clinical Biochemistry, Jagiellonian University Medical College, Kopernika 15a Street, 31-501 Cracow, Poland. urazny@cm-uj.krakow.pl
authors.forename: Urszula
authors.initials: U
authors.lastname: Razny
authors.forename: Beata
authors.initials: B
authors.lastname: Kiec-Wilk
authors.forename: Lukasz
authors.initials: L
authors.lastname: Wator
authors.forename: Anna
authors.initials: A
authors.lastname: Polus
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Dyduch
authors.forename: Bogdan
authors.initials: B
authors.lastname: Solnica
authors.forename: Maciej
authors.initials: M
authors.lastname: Malecki
authors.forename: Romana
authors.initials: R
authors.lastname: Tomaszewska
authors.forename: John P
authors.initials: JP
authors.lastname: Cooke
authors.forename: Aldona
authors.initials: A
authors.lastname: Dembinska-Kiec
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001823:Body Composition / Q000187:drug effects / Q000502:physiology; D004041:Dietary Fats / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000172:deficiency / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology
chemical_list: D004041:Dietary Fats; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III