title: Altered glucose and lipid homeostasis in liver and adipose tissue pre-dispose inducible NOS knockout mice to insulin resistance.
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.
authors.affiliation: Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow - 226031, India.|Academy of Scientific and Innovative Research, New Delhi - 110001, India.
authors.forename: Babu Nageswararao
authors.initials: BN
authors.lastname: Kanuri
authors.affiliation: Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow - 226031, India.
authors.forename: Jitendra S
authors.initials: JS
authors.lastname: Kanshana
authors.affiliation: Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow - 226031, India.
authors.forename: Sanjay C
authors.initials: SC
authors.lastname: Rebello
authors.affiliation: Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow - 226031, India.
authors.forename: Priya
authors.initials: P
authors.lastname: Pathak
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow - 226031, India.
authors.forename: Anand P
authors.initials: AP
authors.lastname: Gupta
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow - 226031, India.
authors.forename: Jiaur R
authors.initials: JR
authors.lastname: Gayen
authors.affiliation: Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow - 226031, India.
authors.forename: Kumaravelu
authors.initials: K
authors.lastname: Jagavelu
authors.affiliation: Academy of Scientific and Innovative Research, New Delhi - 110001, India.
authors.forename: Madhu
authors.initials: M
authors.lastname: Dikshit
mesh_terms: D000273:Adipose Tissue / Q000503:physiopathology*; D000818:Animals; D050218:Body Fat Distribution; D001835:Body Weight; D004032:Diet / Q000379:methods; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008099:Liver / Q000503:physiopathology*; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000172:deficiency*; D010101:Oxygen Consumption; D012119:Respiration; D022722:Thermogenesis
chemical_list: D052247:Nitric Oxide Synthase Type II; D005947:Glucose