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

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Cardiovascular Diabetology

, 10:68

First Online: 22 July 2011Received: 01 June 2011Accepted: 22 July 2011


BackgroundHigh 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.

MethodseNOS- 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.

ResultseNOS- 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.

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

KeywordseNOS- mice DDAH mice microarray adipogenesis angiogenesis List of AbbreviationsADMAasymmetric dimethylarginine

AMPK5- adenosine monophosphate-activated protein kinase

BATbrown adipose tissue

bFGFbasic fibroblast growth factor

cGMPcyclic guanosine monophosphate

DDAHdimethylarginine dimethylaminohydrolase

eNOS- miceendothelial nitric oxide deficient mice

FFAfree fatty acids

HFDhigh fat diet

HGFhepatocyte growth factor

Hsp90heat shock protein 90

IGF-1insulin - like growth factor

IL-6interleukin 6


L-NAMENG-nitro-L-arginine methyl ester

NOnitric oxide

NOSnitric oxide synthase

PECAM-1 CD31platelet-endothelial cell adhesion molecule 1

PPARαperoxisome proliferator-activated receptor α

TNF-αtumor necrosis factor α

VEGFvascular endothelial growth factor

WATwhite adipose tissue

WT micewild type mice.

Electronic supplementary materialThe online version of this article doi:10.1186-1475-2840-10-68 contains supplementary material, which is available to authorized users.

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Author: Urszula Razny - Beata Kiec-Wilk - Lukasz Wator - Anna Polus - Grzegorz Dyduch - Bogdan Solnica - Maciej Malecki - Romana T


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