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

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.

High-fat diet-induced kidney alterations in rats with metabolic syndrome: endothelial dysfunction and decreased antioxidant defense.

INTRODUCTION: This study aimed to investigate changes in renal function and the AGE-RAGE axis in the kidney of a non-genetic animal model of metabolic syndrome (MetS) induced by high-fat diet (HFD). Additionally, we evaluated the protective effect of pyridoxamine (PM), a vitamin B6 analog with anti-AGE effects, in the context of diet-related renal endothelial dysfunction. METHODOLOGY: In Wistar rats, the MetS animal model was induced by 20 or 28 weeks of HFD feeding. When indicated, a subgroup of animals was treated daily with PM (60 mg/kg) for 2 months. Tissue perfusion in renal microcirculation was examined by laser speckle contrast imaging. Oxidative stress was analyzed by thiobarbituric acid reactive species and the inflammatory markers by ELISA (TNF-α and IL-1ß). Reverse transcription polymerase chain reaction was used to analyze eNOs, IL-6, vascular cell adhesion molecule (VCAM), NADPH oxidase subunit 47 (N47), catalase, and receptor for AGE (RAGE) gene expression. RESULTS: Wistar rats fed a HFD showed negligible alteration in renal function, decrease in catalase mRNA transcripts and catalase enzyme activity compared to control (CTL) animals. Increased levels of IL-1ß were observed in the kidney of MetS-induced rats. HFD-fed rats exhibited kidney endothelial dysfunction, with no significant differences in basal microvascular blood flow. PM significantly improved kidney vasorelaxation in HFD-fed rats. eNOS, VCAM, and RAGE gene expression and AGE content were not altered in kidneys of HFD-induced MetS rats in comparison to CTLs. CONCLUSIONS: Our findings suggest that HFD-induced microvascular dysfunction precedes the decline in renal function, and could be related to antioxidant machinery defects and inflammation activation in the kidney. PM showed a vasoprotective effect, and thus, could be an important contributory factor in ameliorating diet-induced renal damage.