Abstract
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 (VCO2), 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.
Highlights
Nitric oxide (NO), an important gaseous signaling molecule, regulates numerous physiological processes having its synthesis being regulated by Ca+2 dependent nitric oxide synthases and/or Ca+2 independent inducible nitric oxide synthase[1,2]
The present study was undertaken to address the anomalies in the role of inducible nitric oxide synthase (iNOS) in the incidence of insulin resistance (IR) by using WT and iNOS KO mice fed on low fat diet (LFD) for 5 weeks
Our results demonstrate the incidence of tissue specific and systemic IR as a resultant of reduced NO availability in iNOS KO mice fed with LFD for 5 weeks
Summary
Nitric oxide (NO), an important gaseous signaling molecule, regulates numerous physiological processes having its synthesis being regulated by Ca+2 dependent nitric oxide synthases (eNOS and nNOS) and/or Ca+2 independent inducible nitric oxide synthase (iNOS)[1,2]. High fat diet (HFD) fed obese (DIO) and ob/ob mice exhibited elevated iNOS expression in liver, skeletal muscle and adipose tissue[5,6] and the inactivation of insulin receptor β/insulin receptor substrate-1 (IRS-1) and AKT11,12. Parameters related to energy homeostasis such as food intake, energy utilization and physical activity, and genes responsible for glucose and lipid metabolism were not profiled in these studies[17,20] These contradictory outcomes associated with iNOS studies and IR could be due to the use of variable protocols such as amount of glucose (1–2 g) and insulin (0.35 to 1.5 IU) administered for monitoring the tolerance, duration of fasting (4–12 h), glucose/insulin levels and the types of diets (10–60% kcal in energy)[17,20]. Our results demonstrate the incidence of tissue specific (liver and adipose tissue but not skeletal muscle) and systemic IR as a resultant of reduced NO availability in iNOS KO mice fed with LFD for 5 weeks
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
