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Increased nitric oxide availability attenuates high fat diet metabolic alterations and gene expression associated with insulin resistance

Urszula Razny1*, Beata Kiec-Wilk13, Lukasz Wator1, Anna Polus1, Grzegorz Dyduch2, Bogdan Solnica1, Maciej Malecki3, Romana Tomaszewska2, John P Cooke4 and Aldona Dembinska-Kiec1

Author Affiliations

1 Department of Clinical Biochemistry, Jagiellonian University Medical College, Kopernika 15a Street, 31-501 Cracow, Poland

2 Department of Pathomorphology, Jagiellonian University Medical College, Grzegorzecka 16 Street, 31-531 Cracow, Poland

3 Department of Metabolic Diseases, Jagiellonian University Medical College, Kopernika 15 Street, 31-501 Cracow, Poland

4 Stanford University School of Medicine, 300 Pasteur Dr., Stanford, CA 94305-5406, USA

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Cardiovascular Diabetology 2011, 10:68  doi:10.1186/1475-2840-10-68

Published: 22 July 2011



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.


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.


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.


Our results indicate that increased NO availability attenuates some HFD induced alterations in metabolism and gene expression associated with insulin resistance.

eNOS-/- mice; DDAH mice; microarray; adipogenesis; angiogenesis