| Autor: |
Kanuri BN; a Division of Pharmacology , Central Drug Research Institute, Council of Scientific and Industrial Research , Lucknow , India.; b Academy of Scientific and Innovative Research , New Delhi , India., Rebello SC; a Division of Pharmacology , Central Drug Research Institute, Council of Scientific and Industrial Research , Lucknow , India., Pathak P; a Division of Pharmacology , Central Drug Research Institute, Council of Scientific and Industrial Research , Lucknow , India., Agarwal H; a Division of Pharmacology , Central Drug Research Institute, Council of Scientific and Industrial Research , Lucknow , India., Kanshana JS; a Division of Pharmacology , Central Drug Research Institute, Council of Scientific and Industrial Research , Lucknow , India., Awasthi D; a Division of Pharmacology , Central Drug Research Institute, Council of Scientific and Industrial Research , Lucknow , India., Gupta AP; c Division of Pharmacokinetics and Metabolism , Central Drug Research Institute, Council of Scientific and Industrial Research , Lucknow , India., Gayen JR; c Division of Pharmacokinetics and Metabolism , Central Drug Research Institute, Council of Scientific and Industrial Research , Lucknow , India., Jagavelu K; a Division of Pharmacology , Central Drug Research Institute, Council of Scientific and Industrial Research , Lucknow , India., Dikshit M; d Bioscience and Bioengineering , Indian Institute of Technology Jodhpur , Jodhpur , India. |
| Abstrakt: |
Oxidative stress due to enhanced production or reduced scavenging of reactive oxygen species (ROS) has been associated with diet (dyslipidemia) induced obesity and insulin resistance (IR). The present study was undertaken to assess the role of p47 phox in IR using wild type (WT) and p47 phox-/- mice, fed with different diets (HFD, LFD or Chow). Augmented body weight, glucose intolerance and reduced insulin sensitivity were observed in p47 phox-/- mice fed with 45% HFD and 10% LFD. Further, body fat and circulating lipids were increased significantly with 5 weeks LFD feeding in p47 phox-/- mice, while parameters of energy homeostasis were reduced as compared with WT mice. LFD fed knockout (KO) mice showed an enhanced hepatic glycogenolysis, and reduced insulin signalling in liver and adipose tissue, while skeletal muscle tissue remained unaffected. A significant increase in hepatic lipids, adiposity, as well as expression of genes regulating lipid synthesis, breakdown and efflux were observed in LFD fed p47 phox-/- mice after 5 weeks. On the other hand, mice lacking p47 phox demonstrated altered glucose tolerance and tissue insulin sensitivity after 5 weeks chow feeding, while changes in body weight, respiratory exchange ratio (RER) and heat production are non-significant. Our data demonstrate that lack of p47 phox is sufficient to induce IR through altered glucose and lipid utilization by the liver and adipose tissue. |
