Increased total DNA damage and oxidative stress in brain are associated with decreased longevity in high sucrose diet fed WNIN/Gr-Ob obese rats

Abstract

Background: Obesity and Type 2 Diabetes (T2D) are chronic nutrient-related disorders that occur together and pose a grave burden to society. They are among the most common causes of ageing and death. Obesity and T2D per se accelerate ageing albeit the underlying mechanisms are unclear yet. Also, it is not clear whether or not superimposing T2D on obesity accelerates ageing. Present study validated the hypothesis, ‘super-imposing T2D on obesity accelerates ageing’ in WNIN/Gr-Ob, the impaired glucose tolerant, obese rat as the model and evaluated probable underlying mechanisms.

Objectives: To estimate the survival analysis of WNIN/Gr-Ob rats induced with T2D. To determine the extent of DNA damage and oxidative stress in the brain, the master controller of the body, in WNIN/Gr-Ob rats with/without high sucrose induced T2D/aggravation of insulin resistance (IR) after 3 and 6 months of feeding.

Methods: T2D was induced/IR was aggravated by feeding high sucrose diet (HSD) to 9–10 weeks old, male WNIN/Gr-Ob rats. Survival percentage was determined statistically by Kaplan–Meier estimator. Neuronal DNA damage was quantified by the Comet assay while the oxidative stress and antioxidant status were evaluated from the levels of malonaldialdehyde, reduced glutathione, and superoxide dismutase (SOD) activity.

Results and Discussion: HSD feeding decreased longevity of WNIN/Gr-Ob rats and was associated with significantly higher total neuronal DNA damage after three months of feeding but not later. In line with this was the increased neuronal oxidative stress (lipid peroxidation) and decreased antioxidant status (reduced glutathione and SOD activity) in HSD than Starch-based diet (SBD) fed rats. The results suggest that HSD feeding decreased the longevity of WNIN/Gr-Ob obese rats probably by increasing oxidative stress and aggravating IR, a condition that precedes T2D.

Keywords:

• DNA damage
• Neurons
• Insulin resistance
• Oxidative stress
• High sucrose diet
• WNIN/Gr-Ob obese rats
• Ageing

Acknowledgements

We acknowledge DBT for funding the project (BT/PR3404/FNS/20/529/2011), NIN/NCLAS (ICMR) for the supply of animals. We thank Mrs Malathi for extending her assistance in maintaining animals and running assays.

Disclaimer statements

Contributors None.

Funding This work was supported by Department of Biotechnology, Ministry of Science and Technology: [Grant Number BT/PR3404/FNS/20/529/2011].

Conflicts of interest None.

Ethics approval The animal experimental procedure was approved by the ‘Institute's ethical committee on animal experiments’ at National Institute of Nutrition, Hyderabad, India (P10/NCLAS/IAEC-25/7/2012).