The Effect of High-Intensity Interval Training on Reducing Inducible Nitric Oxide Synthase Gene Expression in Visceral Adipose Tissue of Diabetic Rats Fed a High-Fat Diet

Abstract

Background and Aim: Considering the role of exercise in controlling Diabetes and its complications and the lack of clarity on the molecular mechanism affecting Diabetes, the aim of the present study was to compare the effectiveness of two types of high- intensity interval training and continuous endurance training on the expression of the inducible nitric oxide synthase gene in visceral adipose tissue of diabetic rats.

Materials and Methods: In this experimental study, 45 Wistar rats (200±10 g) were randomly divided into non-diabetic, diabetic, continuous endurance training and high-intensity interval training groups after induction of Diabetes by a high-fat diet. The exercise program was implemented for ten weeks. A continuous endurance training program was performed, consisting of 30 minutes of running at 50 to 60% of VO2 max. A high-intensity interval training program was performed as five two-minute intervals of running at 80 to 90% of VO2 max and one minute of rest at 30 to 35% of VO2 max. The expression level of the inducible nitric oxide synthase gene in visceral adipose tissue was measured by qReal Time Polymerase Chain Reaction, its expression at the protein level was measured by Western blot, and plasma glucose levels were measured by glucose oxidase.

Result: The results demonstrated that the induction of diabetes led to elevated blood glucose levels and an altered lipid profile (cholesterol and triglycerides) compared to the control group. Furthermore, the exercise intervention resulted in reduced blood glucose and improved lipid profiles in both exercise groups. The HIIT (High-Intensity Interval Training) group showed more effective improvements in plasma glucose and lipid profiles than the CET (Continuous Endurance Training) group. Both the HIIT and CET groups exhibited significant reductions in plasma glucose concentration compared to the diabetic control (DC) group (reductions of 53% and 35%, respectively; P<0.001). Additionally, the magnitude of this reduction was greater in the HIIT group than in the CET group (P<0.001). The high-fat diet induced a 2.7-fold increase in iNOS gene expression (P<0.001). Both exercise interventions resulted in a reduction of iNOS gene expression in the CET and HIIT groups by 40% and 54%, respectively (P<0.05). Notably, a greater reduction in iNOS mRNA expression was observed in the HIIT group compared to the CET group (P<0.05). Western blot analysis of iNOS expression at the protein level revealed that the high-fat diet significantly induced a 2.3-fold increase in iNOS protein expression. Both exercise interventions significantly reduced the diet-induced iNOS expression; furthermore, the HIIT intervention was more potent in reducing iNOS expression. The CET and HIIT interventions resulted in reductions of 42% and 51%, respectively (P<0.05).

Conclusion: It seems that exercise training, especially high-intensity interval training, probably due to higher intensity, may be a more effective intervention for reducing inducible nitric oxide synthase gene expression at the Messenger Ribonucleic Acid and protein levels and reducing blood glucose in diabetic patients, and it can be one of the effective factors in preventing M1/M2 polarization of adipose tissue macrophages.