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: Urszula Razny, Beata Kiec-Wilk, Lukasz Wator, Anna Polus, Grzegorz Dyduch, Bogdan Solnica, Maciej Malecki, Romana Tomaszewska, John P Cooke, Aldona Dembinska-Kiec
• Journal: Cardiovascular diabetology (Cardiovasc Diabetol) Vol. 10 Pg. 68 (Jul 22 2011) ISSN: 1475-2840 [Electronic] England
• PMID: 21781316 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Dietary Fats
• Nitric Oxide
• Nitric Oxide Synthase Type III

Topics

• Adipose Tissue (drug effects, metabolism)
• Animals
• Body Composition (drug effects, physiology)
• Dietary Fats (metabolism, pharmacology)
• Female
• Gene Expression Regulation (drug effects, physiology)
• Insulin Resistance (physiology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Transgenic
• Models, Animal
• Neovascularization, Physiologic (drug effects, physiology)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type III (deficiency, genetics)
• Oxidative Stress (drug effects, physiology)