Aerobic training prevents oxidative profile and improves nitric oxide and vascular reactivity in rats with cardiometabolic alteration.

What is the central question of this study? What are the effects of exercise training on the hepatic renin-angiotensin system and their contribution to damage resulting from fructose overload in rats? What is the main finding and its importance? Exercise training attenuated the deleterious actions of the angiotensin-converting enzyme/angiotensin II/angiotensin II type 1 receptor axis and increased expression of the counter-regulatory (angiotensin-converting enzyme 2/angiotensin (1-7)/Mas receptor) axis in the liver. Therefore, our study provides evidence that exercise training modulates the hepatic renin-angiotensin system, which contributes to reducing the progression of metabolic dysfunction and non-alcoholic fatty liver disease in fructose-fed rats. The renin-angiotensin system (RAS) has been implicated in the development of metabolic syndrome. We investigated whether the hepatic RAS is modulated by exercise training and whether this modulation improves the deleterious effects of fructose overload in rats. Male Wistar rats were divided into (n = 8 each) control (CT), exercise control (CT-Ex), high-fructose (HFr) and exercise high-fructose (HFr-Ex) groups. Fructose-drinking rats received d-fructose (100 g l ). After 2 weeks, CT-Ex and HFr-Ex rats were assigned to a treadmill training protocol at moderate intensity for 8 weeks (60 min day , 4 days per week). We assessed body mass, glucose and lipid metabolism, hepatic histopathology, angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) activity, the angiotensin concentration and the expression profile of proteins affecting the hepatic RAS, gluconeogenesis and inflammation. Neither fructose overload nor exercise training influenced body mass gain and serum ACE and ACE2 activity. The HFr group showed hyperinsulinaemia, but exercise training normalized this parameter. Exercise training was effective in preventing hepatic steatosis and in preventing triacylglycerol and glycogen accumulation. Furthermore, exercise improved the response to the deleterious effects of HFr overload by normalizing the gluconeogenesis pathway and the protein levels of interleukin-6 and tumour necrosis factor-α. The HFr rats displayed increased hepatic ACE activity and protein expression and angiotensin II concentration, which were attenuated by exercise training. Exercise training restored the ACE2/angiotensin-(1-7)/Mas receptor axis. Exercise training may favour the counter-regulatory ACE2/angiotensin-(1-7)/Mas receptor axis over the classical RAS (ACE/angiotensin II/angiotensin II type 1 receptor axis), which could be responsible for the reduction of metabolic dysfunction and the prevention of non-alcoholic fatty liver disease.

Scope: Perinatal maternal obesity and excessive fructose consumption have been associated with liver metabolic diseases. The study investigates whether moderate maternal high-fat diet affects the liver mitochondria responses to fructose intake in adult offspring. Methods and Results: Wistar female rats have received a standard diet (mSTD) or high-fat diet (mHFD) (9% and 28.6% fat, respectively), before mating until the end of lactation. Male offspring were fed standard diet from weaning to adulthood and received water or fructose-drinking water (15%) from 120 to 150 days old. Fructose induces liver mitochondrial ultrastructural alterations with higher intensity in mHFD offspring, accompanied by reduced autophagy markers. Isolated mitochondria respirometry shows unaltered ATP-coupled oxygen consumption with increased Atp5f1b mRNA only in mHFD offspring. Fructose increases basal respiration and encoding complex I-III mRNA, only in mSTD offspring. Uncoupled respiration is lower in mHFD mitochondria that are unable to exhibit fructose-induced increase Ucp2 mRNA. Fructose decreases antioxidative defense markers, increases unfolded protein response and insulin resistance only in mHFD offspring without fructose-induced hepatic lipid accumulation. Conclusion: Mitochondrial dysfunction and homeostatic disturbances in response to fructose are early events evidencing the higher risk of fructose damage in the liver of adult offspring from dams fed an isocaloric moderate high-fat diet.

Endothelial function is a key mechanism in the development of CVD. Arginine and exercise are important non-pharmacological strategies for mitigating the impact of metabolic changes in the metabolic syndrome, but the effect of their combined administration is unknown. Thus, the aim of this study was to investigate the isolated and combined effects of aerobic training and arginine supplementation on metabolic variables and vascular reactivity in rats at high risk for developing the metabolic syndrome. Wistar rats were divided into two groups: control and fructose (F - water with 10 % fructose). After 2 weeks, the F group was divided into four groups: F, fructose+arginine (FA, 880 mg/kg per d of l-arginine), fructose+training (FT) and fructose+arginine+training (FTA); treatments lasted for 8 weeks, and no difference was observed in body mass gain. Arginine did not improve the body protein content, and both the FA and FT groups show a reversal of the increase in adipose tissue. Insulin increase was prevented by training and arginine, without additive effect, and the increase in serum TAG was prevented only by training. The F group showed impaired endothelium-dependent vasodilation and hyperreactivity to phenylephrine, but arginine and training were capable of preventing these effects, even separately. Higher nitric oxide level was observed in the FA and FT groups, and no potentiating effect was detected. Thus, only training was able to prevent the increase in TAG and improve the protein mass, and training and arginine exert similar effects on fat content, insulin and endothelial function, but these effects are not additive.

Neuromedin B (NB) and gastrin-releasing peptide (GRP) are bombesin-like peptides, found in the gastrointestinal tube and pancreas, among other tissues. Consistent data proposed that GRP stimulates insulin secretion, acting directly in pancreatic cells or in the release of gastrointestinal hormones that are incretins. However, the role of NB remains unclear. We examined the glucose homeostasis in mice with deletion of NB receptor (NBR-KO). Female NBR-KO exhibited similar fasting basal glucose with lower insulinemia (48.4%) and lower homeostasis model assessment of insulin resistance index (50.5%) than wild type (WT). Additionally, they were more tolerant to oral glucose, demonstrated by a decrease in the area under the glucose curve (18%). In addition, 15 min after an oral glucose load, female and male NBR-KO showed lower insulin serum levels (45.6 and 26.8%, respectively) than WT, even though blood glucose rose to similar levels in both groups. Single injection of NB, one hour before the oral glucose administration, tended to induce higher serum insulin in WT (28.9%, p=0.3), however the same did not occur in NBR-KO. They showed no changes in fasting insulin content in pancreatic islets by immunohistochemistry, however, the fasting serum levels of glucagon-like peptide, a potent incretin, exhibited a strong trend to reduction (40%, p=0.07). Collectively, mice with deletion of NB receptor have lower insulinemia, especially in response to oral glucose, and females also exhibited a better glucose tolerance, suggesting the involvement of NB and its receptor in regulation of insulin secretion induced by incretins, and also, in insulin sensitivity.

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The present study demonstrates that maternal cinnamon intake during lactation promotes mild changes in dams and can trigger sex-specific metabolic programming in pups that lasts into adulthood. © 2017 Society of Chemical Industry.