Karen Jesus Oliveira

Central NPY-Y5 receptors activation plays a major role in fasting-induced pituitary-thyroid axis suppression in adult rat.

Neuropeptide Y (NPY) inhibits TRH neurons in fed state, and hypothalamic NPY higher expression during fasting has been proposed to be involved in fasting-induced suppression of the hypothalamus-pituitary-thyroid (HPT) axis. We investigated the role of central Y5 receptors in the control of thyrotropin (TSH) and thyroid hormone (TH) secretion. Fed and fasting rats received twice daily central injections (3rd ventricle) of Y5 receptor antagonist (CGP71683; 15nmol/rat) for 72h. Fasted rats also received a single central injection of CGP71683 (15nmol/rat) at the end of 72h of fasting. In fed rats, Y5 receptor blockade reduced total food intake by 32% and body mass by almost 10% (p<0.01), corroborating the role of this receptor in food intake control. 72h-fasted rats exhibited a 4-fold increase in serum TSH (p<0.001), 1h after a single injection of Y5 antagonist. Also with multiple injections during 72h of fasting, Y5 blockade resulted in activation of thyroid axis, as demonstrated by a 3-times rise in serum T4 (p<0.001), accompanied by unchanged TSH and T3. In fed rats, the chronic central administration of CGP71683 resulted in reduced total serum T4 without changes in free T4 and TSH. Serum leptin and PYY were not altered by the NPY central blockade in both fed and fasted rats, suggesting no role of these hormones in the alterations observed. Therefore, the inhibition of central Y5 neurotransmission resulted in activation of thyroid axis during fasting suggesting that NPY-Y5 receptors contribute to fasting-induced TSH and TH suppression.

Exercise training modulates the hepatic renin-angiotensin system in fructose-fed rats

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.

Ageing is associated with brown adipose tissue remodelling and loss of white fat browning in female C57BL/6 mice

Fat storage changes throughout life and affects body metabolism. Ageing impact on brown (BAT) and white adipose tissue (WAT) deserves attention, especially in females, because they are less prone to age‐induced weight gain. While in male mice the impact of ageing on adipose tissue remodelling is well characterized, the effects in female mice remain largely unclear. Thus, we investigated BAT and WAT remodelling during ageing in female C57BL/6 mice. At 3 months, body weight was 24 ± 0.3 g (mean±SD), and it increased from 6 to 9 months of age (+20%, P < 0.0001). Oral glucose tolerance test showed no disturbance of glucose metabolism. All WAT depots became heavier, and white adipocytes hypertrophied. The subcutaneous and visceral WAT had clusters of beige cells in younger mice, but they were progressively lost by ageing, indicating loss of WAT browning. Older mice had hypertrophied classic brown adipocytes that had larger cytoplasmic lipid droplets than younger mice. Pearsons correlation showed that WAT mass has a weak correlate with BAT mass, although white adipocyte diameter has a strong correlation with classic brown adipocyte size. In conclusion, our results indicate that female C57BL/6 mice have a progressive age‐dependent loss of subcutaneous and visceral WAT browning, and this process runs in parallel with BAT morphological changes towards a fat storer phenotype, independent of cycling or disturbances in glucose metabolism.

Cinnamon intake reduces serum T3 level and modulates tissue‐specific expression of thyroid hormone receptor and target genes in rats

BACKGROUND Cinnamon has several effects on energy metabolism. However, no data exist on the impact of cinnamon intake on thyroid hormone serum concentrations and action, since thyroid hormones (THs) play a major role in metabolism. RESULTS Male rats were treated with cinnamon water extract (400 mg kg(-1) body weight, 25 days). Cinnamon supplementation resulted in a lower serum total T3 level accompanied by normal serum T4 and TSH levels. The cinnamon-treated rats did not exhibit significant differences in TSHβ subunit, TRβ or deiodinase type 2 mRNA expression in the pituitary. In the liver, cinnamon did not change the TRβ protein expression or the deiodinase type 1 mRNA expression, suggesting that there were no changes in T3 signaling or metabolism in this organ. However, mitochondrial GPDH, a target gene for T3 in the liver, exhibited no changes in mRNA expression, although its activity level was reduced by cinnamon. In the cardiac ventricle, T3 action was markedly reduced by cinnamon, as demonstrated by the lower TRα mRNA and protein levels, reduced SERCA2a and RyR2 and increased phospholamban mRNA expression. CONCLUSION This study has revealed that TH action is a novel target of cinnamon, demonstrating impairment of T3 signaling in the cardiac ventricles.

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

Cardiovascular disease is the major cause of death worldwide; therefore it is important to understand the natural history of the pathophysiologic process and develop strategies to halt its progression. Thus this study investigated the protective effect of aerobic training on pathophysiological mechanisms involved in subclinical cardiometabolic alterations in a model with constant exposure to a prejudicial agent. Male Wistar rats were divided into a control group (C), which received drinking water, fructose group (F), which was fed 10% fructose in drinking water for 10 wk, and control training (CT) and fructose training groups (FT), in which moderate aerobic training was added in the last 8 wk of the study. Insulin, triacylglycerol, and isoprostane were higher and superoxide dismutase (SOD) was lower in the F group. There was no difference in thoracic aorta histology, but a decreased vascularization was seen in the F group, avoided by training in left ventricle. Regarding vascular function, the F group exhibited increased vasoconstrictory reactivity to phenylephrine. The F group presented impaired vasodilation to acetylcholine. Regarding endothelial nitric oxide synthase (eNOS), the F group presented a lower expression, and phosphorylated eNOS was higher in the trained groups than in their respective control groups. This same pattern was observed for nitric oxide bioavailability, antioxidant protein expression in aorta, left ventricle, and muscle (catalase, SOD, and glutathione peroxidase), serum SOD activity, and muscle mass. These results suggest that exercise training enhanced the antioxidant pathway and, as a consequence, the eNOS pathway, preventing an impairment in vascular vasodilatory capacity.

Maternal cinnamon extract intake during lactation leads to sex-specific endocrine modifications in rat offspring: Maternal cinnamon intake alters offspring physiology in a sex-specific manner

BACKGROUND Cinnamon supplementation has been associated with an improvement in glucose disposal and a reduction in fat mass in type 2 diabetes. Maternal nutrition during lactation impacts the health of the offspring throughout life. We hypothesize that cinnamon intake by lactating rats affects maternal physiology, leading to hormonal and metabolic changes in their offspring. To investigate this hypothesis, dams received aqueous cinnamon extract (400 mg cinnamon kg-1  body mass day-1 ) or water orally, during lactation. RESULTS Maternal cinnamon intake did not affect the body mass gain or food intake of dams or their offspring, although it decreased visceral white adipose tissue mass in dams and in their adult offspring of both sexes. Cinnamon-treated dams exhibited no differences in serum insulin, adiponectin, leptin or estradiol levels, although they presented higher serum progesterone. At weaning, cinnamon male pups exhibited lower insulinemia, whereas cinnamon female pups exhibited lower glycemia. Interestingly, in adulthood, only the female offspring exhibited an altered hormonal profile, with reduced serum leptin, adiponectin and insulin levels accompanied by lower glycemia. CONCLUSION 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.

Arginine and aerobic training prevent endothelial and metabolic alterations in rats at high risk for the development of the metabolic syndrome

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.