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Published on: February 25, 2016
Increased nitric oxide availability attenuates high fat diet metabolic alterations and gene expression associated
Urszula Razny1, Beata Kiec-Wilk, Lukasz Wator
1Department of Clinical Biochemistry, Jagiellonian University Medical College, Kopernika 15a Street, 31-501 Cracow, Poland. urazny@cm-uj.krakow.pl
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.
Insights
Increased nitric oxide (NO) bioavailability helps mitigate high-fat diet-induced metabolic changes and insulin resistance. This study shows higher NO levels improve glucose regulation and adipokine profiles in mice on a high-fat diet.
Area of Science:
- Metabolic research
- Cardiovascular research
- Endocrinology
Background:
- High-fat diets (HFD) are known to reduce nitric oxide (NO) bioavailability, contributing to insulin resistance.
- The precise relationship between NO availability and metabolic adaptation during HFD is not fully understood.
Purpose of the Study:
- To investigate the impact of altered NO bioavailability on metabolic responses to a HFD.
- To compare the effects in mice with reduced (eNOS-/-) and increased (DDAH overexpressed) NO levels.
Main Methods:
- Mice with varying NO bioavailability (eNOS-/-, DDAH overexpressed, WT) were fed a HFD for 13 weeks.
- Evaluated body weight, serum parameters (adipokines, insulin, glucose, cholesterol), and performed angiogenesis assessment.
- Analyzed adipose tissue gene expression using microarray and Real Time PCR.
Main Results:
- Mice with increased NO availability (DDAH overexpressed) showed improved glucose levels and increased adiponectin.
- eNOS-/- mice exhibited reduced weight gain, while DDAH mice displayed enhanced angiogenic responses.
- Gene expression patterns indicated altered adipocyte differentiation and lipid synthesis pathways in response to NO levels.
Conclusions:
- Elevated NO bioavailability can attenuate certain metabolic dysregulations induced by HFD.
- Increased NO availability shows potential in mitigating HFD-associated insulin resistance markers and altering gene expression profiles.
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