Altered glucose and lipid homeostasis in liver and adipose tissue pre-dispose inducible NOS knockout mice to insulin resistance

On the basis of diet induced obesity and KO mice models, nitric oxide is implied to play an important role in the initiation of dyslipidemia induced insulin resistance. However, outcomes using iNOS KO mice have so far remained inconclusive. The present study aimed to assess IR in iNOS KO mice after...

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Published in:Scientific reports 2017-01, Vol.7 (1), p.41009-41009, Article 41009
Main Authors: Kanuri, Babu Nageswararao, Kanshana, Jitendra S., Rebello, Sanjay C., Pathak, Priya, Gupta, Anand P., Gayen, Jiaur R., Jagavelu, Kumaravelu, Dikshit, Madhu
Format: Article
Language:English
Subjects:
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Adipose tissue
Animal models
Body composition
Body weight
Carbon dioxide
Dyslipidemia
Electron transport
Energy balance
Gene expression
Gluconeogenesis
Glucose
Glucose tolerance
Homeostasis
Humanities and Social Sciences
Insulin
Insulin resistance
Lipid metabolism
Lipids
Liver
Mitochondria
multidisciplinary
Nitric oxide
Nitric-oxide synthase
Nitrites
Oxygen consumption
Rodents
Science
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Summary:On the basis of diet induced obesity and KO mice models, nitric oxide is implied to play an important role in the initiation of dyslipidemia induced insulin resistance. However, outcomes using iNOS KO mice have so far remained inconclusive. The present study aimed to assess IR in iNOS KO mice after 5 weeks of LFD feeding by monitoring body composition, energy homeostasis, insulin sensitivity/signaling, nitrite content and gene expressions changes in the tissues. We found that body weight and fat content in KO mice were significantly higher while the respiratory exchange ratio (RER), volume of carbon dioxide (VCO 2 ), and heat production were lower as compared to WT mice. Furthermore, altered systemic glucose tolerance, tissue insulin signaling, hepatic gluconeogenesis, augmented hepatic lipids, adiposity, as well as gene expression regulating lipid synthesis, catabolism and efflux were evident in iNOS KO mice. Significant reduction in eNOS and nNOS gene expression, hepatic and adipose tissue nitrite content, circulatory nitrite was also observed. Oxygen consumption rate of mitochondrial respiration has remained unaltered in KO mice as measured using extracellular flux analyzer. Our findings establish a link between the NO status with systemic and tissue specific IR in iNOS KO mice at 5 weeks.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep41009