The mitochondrial uncoupling proteins (UCPs) of interscapular brown adipose tissue (iBAT) and of muscles play important roles in energy balance. For instance, the expression of UCP1 and UCP3 are modulated by free fatty acid gradients induced by high-sugar diets and acute exercise that is dependent on sympathetic stimulation. However, the effects of endurance training in animals fed with high-sugar diets are unknown. This study aims to evaluate the long-term effects of diet and exercise on UCP1 and UCP3 levels and energy balance efficiency. Rats fed with standard or high-sugar (HSD) diets were simultaneously subjected to running training over an 8-week period. After the training period, the rats were decapitated, and the iBAT and gastrocnemius muscle tissues were removed for evaluation of the β₃-receptor, Ucp1, and Ucp3 mRNA and protein expression, which were analyzed by quantitative reverse transcriptase polymerase chain reaction and Western blot, respectively. Groups fed with an HSD displayed a higher adiposity index and iBAT weight (P < .05), whereas exhibited an up-regulation of Ucp1 mRNA and protein levels (P < .05). Training increased β₃-receptor mRNA in iBAT and reduced the Ucp3 mRNA in muscle tissues. In association with an HSD, training restored the increasing β₃-receptor mRNA and greatly up-regulated the levels of Ucp3 mRNA. Therefore, training blocked the HSD-induced up-regulation of UCP1 expression in iBAT, whereas it up-regulated the expression of Ucp3 mRNA in muscle. These results suggest that training enhances the relationship between Ucp1/Ucp3 mRNA levels, which could result in higher energy efficiency, but not when HSD-induced elevated sympathetic activity is maintained.

The presence of leptin receptors in white adipose tissue (WAT) suggests a type of peripheral control during the development of obesity and other metabolic disorders. Both diet composition and exercise influence serum leptin; however, the effect of their combination on long-term WAT leptin metabolism is unknown. In this study, rats fed with standard or high-sugar diets (HSD) were simultaneously subjected to running training for 4- and 8-week periods, and the retroperitoneal WAT (rWAT) was evaluated for adipocyte cell size, lipid and catecholamine content, Lep, OB-Rb and Ucp2 mRNA transcription levels, and circulating leptin and non-esterified fatty acids (NEFA). The HSD groups displayed a higher adiposity index and rWAT weight, Lep mRNA and protein upregulation, and a period-dependent effect on OB-Rb mRNA expression. Exercise decreased serum leptin and upregulated the OB-Rb mRNA levels. However, in rats fed with an HSD, the increase in OB-Rb mRNA and reduction in catecholamine levels resulted in a high level of adiposity and hyperleptinemia. The combination of training and an HSD decreases the NEFA levels and upregulating the Ucp2 mRNA expression in the 4-week period, while downregulating the Ucp2 mRNA expression in the 8-week period without changing the NEFA levels. Our results suggest that an HSD induces an increase in leptin expression in rWAT, while reducing adipocytes via leptin-mediated lipolysis after an 8-week period. In exercised rats fed an HSD, TAG synthesis and storage overlaps with lipolysis, promoting fat store development and Lep mRNA and plasma protein upregulation in adult rats.

Neurological dysfunction as a result of neuroinflammation has been reported in sepsis and cause high mortality. High levels of cytokines stimulate the formation of neurotoxic metabolites by kynurenine (KYN) pathway. Vitamin B (vit B) has anti-inflammatory and antioxidant properties and also acts as a cofactor for enzymes of the KYN pathway. Thus, by using a relevant animal model of polymicrobial sepsis, we studied the effect of vit B on the KYN pathway, acute neurochemical and neuroinflammatory parameters, and cognitive dysfunction in rats. Male Wistar rats (250-300 g) were submitted to cecal ligation and perforation (CLP) and divided into sham + saline, sham + vit B, CLP + saline, and CLP + vit B (600 mg/kg, s.c.) groups. Twenty-four hours later, the prefrontal cortex and hippocampus were removed for neurochemical and neuroinflammatory analyses. Animals were followed for 10 days to determine survival rate, when cognitive function was assessed by behavioral tests. Vitamin B interfered in the activation of kynurenine pathway, which led to an improvement in neurochemical and neuroinflammatory parameters and, consequently, in the cognitive functions of septic animals. Thus, the results indicate that vit B exerts neuroprotective effects in acute and late consequences after sepsis.

Resveratrol (RSV) is anti-inflammatory and neuroprotective, cross the blood-brain barrier (BBB) and has a safe profile. Besides, RSV modulates the expression of some miRNAs related to neurological disorders. Thus, we hypothesized that RSV can be neuroprotective in pneumococcal meningitis by modulating the global microRNA expression profile (miRNome). Eleven-day old rats were intracysternally infected with S. pneumoniae (~ 2 × 10 c.f.u.) and were orally administered with RSV (50 mg/kg) or vehicle in pre-treatment (before infection) or post-treatment schedules (3 and 18 h p.i.). At 24 h p.i., animals were euthanized and apoptotic cells were counted in the hippocampal dentate gyrus of the right brain hemispheres. The hippocampi from left hemispheres were used for cytokines and chemokines multiplex assay and miRNome profiling with TaqMan OpenArray Rodent MicroRNA. Infected rats treated with RSV had lower apoptotic scores and IL-1β, CCL, and CCL levels when compared to the infected group receiving placebo. Seven miRNAs were down regulated, and 18 were up regulated by pneumococcal acute meningitis. Thirty-seven miRNAs were down regulated, and three were up regulated (hsa-miR-15b-5p, hsa-miR-25-3p, hsa-miR-125b-5p) by the interaction between meningitis and RSV. Pathway enriched analysis revealed that meningitis and RSV modulate the expression of miRNAs targeting critical pathways related to the pathophysiology of bacterial meningitis. Nevertheless, hsa-miR-25-3p and hsa-miR-125b-5p target the transcription factor TEF-1, for which there are binding sites in Il-1β, Ccl, and Ccl genes. RSV is anti-inflammatory and neuroprotective in an infant rat model of pneumococcal meningitis and these positive effects involve the modulation of the hippocampal miRNome.

Endurance exercise is a remarkable intervention for the treatment of many diseases. Mitochondrial changes on skeletal muscle are likely important for many of the benefits provided by exercise. In this study, we aimed to evaluate the effects that a regular physical activity (swimming without workload) has on mitochondrial morphological alterations and glucometabolic parameters induced by a high-sugar diet (HSD). Weaned male Wistar rats fed with a standard diet or a HSD (68% carbohydrate) were subjected to 60 minutes of regular physical activity by swimming (without workload) for four- (20 sessions) or eight-week (40 sessions) periods. After training, animals were euthanized and the sera, adipose tissues, and skeletal muscles were collected for further analysis. The HSD increased body weight after an 8-week period; it also increased the fat pads and the adipose index, resulting in glucose intolerance and insulin resistance (IR). Transmission electron microscopy showed an increase in alterations of mitochondrial ultrastructure in the gastrocnemius muscle, as well as a decrease in superoxide dismutase (SOD) activity, and an increase in protein carbonylation. Regular physical activity partially reverted these alterations in rats fed a HSD, preventing mitochondrial morphological alterations and IR. Moreover, we observed a decrease in Pgc1α expression (qPCR analysis) in STD-EXE group and a less pronounced reduction in HSD-EXE group after an 8-week period. Thus, regular physical activity (swimming without workload) in rats fed a HSD can prevent mitochondrial dysfunction and IR, highlighting the crucial role for physical activity on metabolic homeostasis.