Glucose and lipid metabolism alterations in liver and adipose tissue pre-dispose p47^phox knockout mice to systemic insulin resistance

Abstract

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.

Keywords:

• Insulin resistance
• reactive oxygen species
• p47^phox
• metabolism

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Acknowledgements

The authors gratefully acknowledge the award of research fellowships by the Council of Scientific and Industrial Research (CSIR), New Delhi, India to K. B. N. and Indian Council of Medical Research, New Delhi, India to J. S. K. The authors are grateful to Mr. M. P. S. Negi, Clinical and Experimental Medicine Division, CSIR-CDRI for helping in the statistical analysis of the data.

Disclosure statement

The authors declare no potential conflict of interest.

Correction Statement

This article was originally published with errors, which have now been corrected in the online version. Please see Correction (http://dx.doi.org/10.1080/10715762.2022.2097607)

Additional information

Funding

The study was supported by a financial grant from Council of Scientific and Industrial Research (CSIR) network project BSC0102 and JC Bose fellowship to MD.