Vasoreactivity of isolated aortic rings from dyslipidemic and insulin resistant inducible nitric oxide synthase knockout mice

Pathak, Priya; Kanshana, Jitendra S.; Kanuri, BabuNageswar; Rebello, Sanjay C.; Aggarwal, Hobby; Jagavelu, Kumaravelu; Dikshit, Madhu

doi:10.1016/j.ejphar.2019.05.005

Cited by 9 publications

(16 citation statements)

References 53 publications

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“…Studies conducted so far on iNOS −/− mice used several dietary fats such as lard or vegetable oils [ 25 , 29 , 32 , 33 , 50 ] among which lard is more obesogenic and diabetogenic [ 51 ]. In addition, dietary regimens and protocols to examine the role of iNOS in IR, obesity, and diabetes [ 25 , 27 , 29 , 33 , 50 ] were also different reporting either IR and dyslipidemia [ 16 , 31 , 32 , 33 ] or protection against IR as outcome [ 25 , 26 , 27 , 28 , 29 , 30 ]. The decreased NO bioavailability in endothelial dysfunction, atherosclerosis, diabetes, obesity, and metabolic syndrome is well established.…”

Section: Discussionmentioning

confidence: 99%

“…Retro-orbital blood was collected from 6 h fasted mice. Estimation of lipids like total cholesterol (TC), triglycerides (TG), low and high density lipoproteins (LDL and HDL), and non-esterified fatty acids (NEFA) were performed in the serum using kits (Randox, Crumlin, Co. Antrim, UK, [ 16 ]). Insulin was measured using a kit from Crystal Chem, Elk Grove Village, IL, USA.…”

Section: Methodsmentioning

confidence: 99%

“…This points towards the protective role of constitutive iNOS in preventing or delaying the pathological alterations in diabetes [ 14 , 15 ]. Studies from our group and others on the effect of iNOS derived NO on endothelium functionality have shown that acetylcholine [ 16 ] and insulin [ 17 ] mediated vasorelaxation was significantly preserved in obese iNOS −/− mice, which was independent of IR, dyslipidemia or hyperglycemia, blood pressure, or oxidative stress. Reduction in NO bioavailability contributes to the pathogenesis of hyperlipidemia, endothelial dysfunction, atherosclerosis, hypertension, diabetes, and obesity [ 18 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 98%

“…Metabolic perturbations and altered insulin sensitivity have been commonly observed in eNOS, nNOS, and triple NOS KO mice [ 21 , 22 , 23 ]. Most of the studies on iNOS −/− mice have demonstrated its definitive role in inflammatory [ 3 , 5 ] and infectious conditions [ 4 , 24 ] whereas inconsistent results were reported for its metabolic role [ 16 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. HFD fed iNOS −/− mice were protected from infiltration of pro-inflammatory macrophages and adipose tissue fibrosis [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

“…Likewise, iNOS −/− mice on long term HFD feeding exhibited increased adiposity [ 25 , 28 , 29 ], and fasting hyperglycemia despite being protected against systemic IR [ 25 ]. Our previous studies on LFD or HFD diet fed iNOS −/− mice found them to be IR and also exhibiting perturbed metabolic homeostasis [ 16 , 32 , 37 ]. Additionally, iNOS −/− mice fed on HFD or LFD displayed significant weight gain, higher fat mass, and dyslipidemia with reduced lean mass [ 33 ].…”

Section: Introductionmentioning

confidence: 99%

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Systemic Insulin Resistance and Metabolic Perturbations in Chow Fed Inducible Nitric Oxide Synthase Knockout Male Mice: Partial Reversal by Nitrite Supplementation

et al. 2020

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iNOS, an important mediator of inflammation, has emerged as an important metabolic regulator. There are conflicting observations on the incidence of insulin resistance (IR) due to hyperglycemia/dyslipidemia in iNOS−/− mice. There are reports that high fat diet (HFD) fed mice exhibited no change, protection, or enhanced susceptibility to IR. Similar observations were also reported for low fat diet (LFD) fed KO mice. In the present study chow fed iNOS−/− mice were examined for the incidence of IR, and metabolic perturbations, and also for the effect of sodium nitrite supplementation (50 mg/L). In IR-iNOS−/− mice, we observed significantly higher body weight, BMI, adiposity, blood glucose, HOMA-IR, serum/tissue lipids, glucose intolerance, enhanced gluconeogenesis, and disrupted insulin signaling. Expression of genes involved in hepatic and adipose tissue lipid uptake, synthesis, oxidation, and gluconeogenesis was upregulated with concomitant downregulation of genes for hepatic lipid excretion. Nitrite supplementation restored NO levels, significantly improved systemic IR, glucose tolerance, and also reduced lipid accumulation by rescuing hepatic insulin sensitivity, glucose, and lipid homeostasis. Obesity, gluconeogenesis, and adipose tissue insulin signaling were only partially reversed in nitrite supplemented iNOS−/− mice. Our results thus demonstrate that nitrite supplementation to iNOS−/− mice improves insulin sensitivity and metabolic homeostasis, thus further highlighting the metabolic role of iNOS.

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