Aerobic Exercise Training Improves Microvascular Function and Oxidative Stress Parameters in Diet-Induced Type 2 Diabetic Mice

Abstract

Purpose

Type 2 diabetic (T2D) patients have liver and adipose tissue microcirculation disturbances associated with metabolic dysfunction and disease progression. However, the potential role of aerobic training on hepatic and white adipose tissue (WAT) microcirculation and the underlying mechanisms have not been elucidated to date. Therefore, we investigated the role of aerobic training on liver and WAT microcirculation and AGE-RAGE modulation in T2D mice.

Methods

The control group (CTL) was fed standard chow, and T2D was induced by feeding male C57BL/6 a high-fat, high-carbohydrate diet for 24 weeks. In the following 12 weeks, mice underwent aerobic training (CTL EX and T2D EX groups), or were kept sedentary (CTL and T2D groups). We assessed metabolic parameters, biochemical markers, oxidative damage, the AGE-RAGE axis, hepatic steatosis, hepatic stellate cells activation (HSC) and liver and WAT microcirculation.

Results

Hepatic microcirculation was improved in T2D EX mice which were associated with improvements in body, liver and fat mass, blood pressure, hepatic steatosis and fibrosis, and decreased HSC and AGE-RAGE activation. In contrast, improvement in WAT microcirculation, that is, decreased leukocyte recruitment and increased perfusion, was associated with increased catalase antioxidant activity.

Conclusion

Physical training improves hepatic and adipose tissue microcirculatory dysfunction associated with T2D, likely due to downregulation of AGE-RAGE axis, decreased HSC activation and increased antioxidant activity.

Keywords:

• microcirculation
• physical training
• AGE-RAGE
• hyperglycemia

Acknowledgment

BioRender was used to make Figure 1A.

Disclosure

The authors declare no conflicts of interest for this work.

Additional information

Funding

This research was funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico grant number CNPq 455,384/2014-2 and PAPES/Fiocruz grant number 401,803/2015-5.