Ketogenic diets, exercise performance, and training adaptations.

PURPOSE OF REVIEW: The ketogenic diet has been proposed as a nutritional strategy in sports. This review was undertaken to provide an overview of the recent literature concerning the effects of ketogenic diet on exercise performance and training adaptations. RECENT FINDINGS: Most recent literature on the ketogenic diet and exercise performance showed no beneficial effects, especially for trained individuals. During a period of intensified training, performance was clearly impaired during the ketogenic intervention, while a diet with high carbohydrates maintained physical performance. The main effect of the ketogenic diet resides in metabolic flexibility, inducing the metabolism to oxidize more fat for ATP resynthesis regardless of submaximal exercise intensities. SUMMARY: The ketogenic diet is not a reasonable nutritional strategy, as it has no advantage over normal/high carbohydrate-based diets on physical performance and training adaptations even when used only in a specific training/nutritional periodization stage.

Effects of the ketogenic diet on performance and body composition in athletes and trained adults: a systematic review and Bayesian multivariate multilevel meta-analysis and meta-regression.

This systematic review with meta-analysis aimed to determine the effects of the ketogenic diet (KD) against carbohydrate (CHO)-rich diets on physical performance and body composition in trained individuals. The MEDLINE, EMBASE, CINAHL, SPORTDiscus, and The Cochrane Library were searched. Randomized and non-randomized controlled trials in athletes/trained adults were included. Meta-analytic models were carried out using Bayesian multilevel models. Eighteen studies were included providing estimates on cyclic exercise modes and strength one-maximum repetition (1-RM) performances and for total, fat, and free-fat masses. There were more favorable effects for CHO-rich than KD on time-trial performance (mode [95% credible interval]; -3.3% [-8.5%, 1.7%]), 1-RM (-5.7% [-14.9%, 2.6%]), and free-fat mass (-0.8 [-3.4, 1.9] kg); effects were more favorable to KD on total (-2.4 [-6.2, 1.8] kg) and fat mass losses (-2.4 [-5.4, 0.2] kg). Likely modifying effects on cyclic performance were the subject's sex and VO2max, intervention and performance durations, and mode of exercise. The intervention duration and subjects' sex were likely to modify effects on total body mass. KD can be a useful strategy for total and fat body losses, but a small negative effect on free-fat mass was observed. KD was not suitable for enhancing strength 1-RM or high-intensity cyclic performances.

Short-Term Alterations in Behavior and Astroglial Function After Intracerebroventricular Infusion of Methylglyoxal in Rats.

Methylglyoxal (MG) is a by-product of glycolysis. In pathological conditions, particularly diabetes mellitus, this molecule is unbalanced, causing widespread protein glycation. In addition to protein glycation, other effects resulting from high levels of MG in the central nervous system may involve the direct modulation of GABAergic and glutamatergic neurotransmission, with evidence suggesting that the effects of MG may be related to behavioral changes and glial dysfunction. In order to evaluate the direct influence of MG on behavioral and biochemical parameters, we used a high intracerebroventricular final concentration (3 µM/µL) to assess acute effects on memory and locomotor behavior in rats, as well as the underlying alterations in glutamatergic and astroglial parameters. MG induced, 12 h after injection, a decrease in locomotor activity in the Open field and anxiolytic effects in rats submitted to elevated plus-maze. Subsequently, 36 h after surgery, MG injection also induced cognitive impairment in both short and long-term memory, as evaluated by novel object recognition task, and in short-term spatial memory, as evaluated by the Y-maze test. In addition, hippocampal glutamate uptake decreased and glutamine synthetase activity and glutathione levels diminished during seventy-two hours after infusion of MG. Interestingly, the astrocytic protein, S100B, was increased in the cerebrospinal fluid, accompanied by decreased hippocampal S100B mRNA expression, without any change in protein content. Taken together, these results may improve our understanding of how this product of glucose metabolism can induce the brain dysfunction observed in diabetic patients, as well as in other neurodegenerative conditions, and further defines the role of astrocytes in disease and therapeutics.

Meal and snack patterns of 7-13-year-old schoolchildren in southern Brazil.

OBJECTIVE: The aim of the current study was to identify and describe the meal and snack patterns (breakfast, mid-morning snack, lunch, mid-afternoon snack, dinner and evening snack) of public schoolchildren. DESIGN: Cross-sectional study. Information on the previous day's food intake was obtained through the Web-CAAFE (Food Intake and Physical Activity of Schoolchildren), an interactive questionnaire, which divides daily food consumption into three meals (breakfast, lunch and dinner) and three snacks (mid-morning, mid-afternoon and evening). Each meal contains thirty-one food items and the schoolchildren clicked on the food items consumed in each meal. Factor analysis was used to identify meal and snack patterns. The descriptions of the dietary patterns (DP) were based on food items with factor loads ≥ 0·30 that were considered representative of each DP. SETTING: Schoolchildren, Florianopolis, Brazil. PARTICIPANTS: Children (n 1074) aged 7-13 years. RESULTS: Lunch was the most consumed meal (96·0 %), followed by dinner (86·4 %), breakfast (85·3 %) and mid-afternoon snack (81·7 %). Four DP were identified for breakfast, mid-morning snack, lunch, dinner and evening snack, and three for mid-afternoon snack. Breakfast, lunch and dinner patterns included traditional Brazilian foods. DP consisting of fast foods and sugary beverages were also observed, mainly for the evening snack. CONCLUSIONS: The results of the current study provide important information regarding the meal and snack patterns of schoolchildren to guide the development of nutrition interventions in public health.

GABAA Modulation of S100B Secretion in Acute Hippocampal Slices and Astrocyte Cultures.

Astrocytes are the major glial cells in brain tissue and are involved, among many functions, ionic and metabolic homeostasis maintenance of synapses. These cells express receptors and transporters for neurotransmitters, including GABA. GABA signaling is reportedly able to affect astroglial response to injury, as evaluated by specific astrocyte markers such as glial fibrillary acid protein and the calcium-binding protein, S100B. Herein, we investigated the modulatory effects of the GABAA receptor on astrocyte S100B secretion in acute hippocampal slices and astrocyte cultures, using the agonist, muscimol, and the antagonists pentylenetetrazol (PTZ) and bicuculline. These effects were analyzed in the presence of tetrodotoxin (TTX), fluorocitrate (FLC), cobalt and barium. PTZ positively modify S100B secretion in hippocampal slices and astrocyte cultures; in contrast, bicuculline inhibited S100B secretion only in hippocampal slices. Muscimol, per se, did not change S100B secretion, but prevented the effects of PTZ and bicuculline. Moreover, PTZ-induced S100B secretion was prevented by TTX, FLC, cobalt and barium indicating a complex GABAA communication between astrocytes and neurons. The effects of two putative agonists of GABAA, ß-hydroxybutyrate and methylglyoxal, on S100B secretion were also evaluated. In view of the neurotrophic role of extracellular S100B under conditions of injury, our data reinforce the idea that GABAA receptors act directly on astrocytes, and indirectly on neurons, to modulate astroglial response.

Effects of dexamethasone on the Li-pilocarpine model of epilepsy: protection against hippocampal inflammation and astrogliosis.

BACKGROUND: Temporal lobe epilepsy (TLE) is the most common form of partial epilepsy and is accompanied, in one third of cases, by resistance to antiepileptic drugs (AED). Most AED target neuronal activity modulated by ionic channels, and the steroid sensitivity of these channels has supported the use of corticosteroids as adjunctives to AED. Assuming the importance of astrocytes in neuronal activity, we investigated inflammatory and astroglial markers in the hippocampus, a key structure affected in TLE and in the Li-pilocarpine model of epilepsy. METHODS: Initially, hippocampal slices were obtained from sham rats and rats subjected to the Li-pilocarpine model of epilepsy, at 1, 14, and 56 days after status epilepticus (SE), which correspond to the acute, silent, and chronic phases. Dexamethasone was added to the incubation medium to evaluate the secretion of S100B, an astrocyte-derived protein widely used as a marker of brain injury. In the second set of experiments, we evaluated the in vivo effect of dexamethasone, administrated at 2 days after SE, on hippocampal inflammatory (COX-1/2, PGE2, and cytokines) and astroglial parameters: GFAP, S100B, glutamine synthetase (GS) and water (AQP-4), and K+ (Kir 4.1) channels. RESULTS: Basal S100B secretion and S100B secretion in high-K+ medium did not differ at 1, 14, and 56 days for the hippocampal slices from epileptic rats, in contrast to sham animal slices, where high-K+ medium decreased S100B secretion. Dexamethasone addition to the incubation medium per se induced a decrease in S100B secretion in sham and epileptic rats (1 and 56 days after SE induction). Following in vivo dexamethasone administration, inflammatory improvements were observed, astrogliosis was prevented (based on GFAP and S100B content), and astroglial dysfunction was partially abrogated (based on Kir 4.1 protein and GSH content). The GS decrease was not prevented by dexamethasone, and AQP-4 was not altered in this epileptic model. CONCLUSIONS: Changes in astroglial parameters emphasize the importance of these cells for understanding alterations and mechanisms of epileptic disorders in this model. In vivo dexamethasone administration prevented most of the parameters analyzed, reinforcing the importance of anti-inflammatory steroid therapy in the Li-pilocarpine model and possibly in other epileptic conditions in which neuroinflammation is present.

Methylglyoxal and carboxyethyllysine reduce glutamate uptake and S100B secretion in the hippocampus independently of RAGE activation.

Diabetes is a metabolic disease characterized by high fasting-glucose levels. Diabetic complications have been associated with hyperglycemia and high levels of reactive compounds, such as methylglyoxal (MG) and advanced glycation endproducts (AGEs) formation derived from glucose. Diabetic patients have a higher risk of developing neurodegenerative diseases, such as Alzheimer's disease or Parkinson's disease. Herein, we examined the effect of high glucose, MG and carboxyethyllysine (CEL), a MG-derived AGE of lysine, on oxidative, metabolic and astrocyte-specific parameters in acute hippocampal slices, and investigated some of the mechanisms that could mediate these effects. Glucose, MG and CEL did not alter reactive oxygen species (ROS) formation, glucose uptake or glutamine synthetase activity. However, glutamate uptake and S100B secretion were decreased after MG and CEL exposure. RAGE activation and glycation reactions, examined by aminoguanidine and L-lysine co-incubation, did not mediate these changes. Acute MG and CEL exposure, but not glucose, were able to induce similar effects on hippocampal slices, suggesting that conditions of high glucose concentrations are primarily toxic by elevating the rates of these glycation compounds, such as MG, and by generation of protein cross-links. Alterations in the secretion of S100B and the glutamatergic activity mediated by MG and AGEs can contribute to the brain dysfunction observed in diabetic patients.

Peripheral Levels of AGEs and Astrocyte Alterations in the Hippocampus of STZ-Diabetic Rats.

Diabetic patients and streptozotocin (STZ)-induced diabetes mellitus (DM) models exhibit signals of brain dysfunction, evidenced by neuronal damage and memory impairment. Astrocytes surrounding capillaries and synapses modulate many brain activities that are connected to neuronal function, such as nutrient flux and glutamatergic neurotransmission. As such, cognitive changes observed in diabetic patients and experimental models could be related to astroglial alterations. Herein, we investigate specific astrocyte changes in the rat hippocampus in a model of DM induced by STZ, particularly looking at glial fibrillary acidic protein (GFAP), S100B protein and glutamate uptake, as well as the content of advanced glycated end products (AGEs) in serum and cerebrospinal fluid (CSF), as a consequence of elevated hyperglycemia and the content of receptor for AGEs in the hippocampus. We found clear peripheral alterations, including hyperglycemia, low levels of proinsulin C-peptide, elevated levels of AGEs in serum and CSF, as well as an increase in RAGE in hippocampal tissue. We found specific astroglial abnormalities in this brain region, such as reduced S100B content, reduced glutamate uptake and increased S100B secretion, which were not accompanied by changes in GFAP. We also observed an increase in the glucose transporter, GLUT-1. All these changes may result from RAGE-induced inflammation; these astroglial alterations together with the reduced content of GluN1, a subunit of the NMDA receptor, in the hippocampus may be associated with the impairment of glutamatergic communication in diabetic rats. These findings contribute to understanding the cognitive deficits in diabetic patients and experimental models.

Increase of extracellular glutamate concentration increases its oxidation and diminishes glucose oxidation in isolated mouse hippocampus: reversible by TFB-TBOA.

Glutamate concentration at the synaptic level must be kept low in order to prevent excitotoxicity. Astrocytes play a key role in brain energetics, and also astrocytic glutamate transporters are responsible for the vast majority of glutamate uptake in CNS. Experiments with primary astrocytic cultures suggest that increased influx of glutamate cotransported with sodium at astrocytes favors its flux to the tricarboxylic acid cycle instead of the glutamate-glutamine cycle. Although metabolic coupling can be considered an emergent field of research with important recent discoveries, some basic aspects of glutamate metabolism still have not been characterized in brain tissue. Therefore, the aim of this study was to investigate whether the presence of extracellular glutamate is able to modulate the use of glutamate and glucose as energetic substrates. For this purpose, isolated hippocampi of mice were incubated with radiolabeled substrates, and CO2 radioactivity and extracellular lactate were measured. Our results point to a diminished oxidation of glucose with increasing extracellular glutamate concentration, glutamate presumably being the fuel, and might suggest that oxidation of glutamate could buffer excitotoxic conditions by high glutamate concentrations. In addition, these findings were reversed when glutamate uptake by astrocytes was impaired by the presence of (3S)-3-[[3-[[4-(trifluoromethyl)benzoyl]amino]phenyl]methoxy]-L-aspartic acid (TFB-TBOA). Taken together, our findings argue against the lactate shuttle theory, because glutamate did not cause any detectable increase in extracellular lactate content (or, presumably, in glycolysis), because the glutamate is being used as fuel instead of going to glutamine and back to neurons.

Dietary n-3 long-chain polyunsaturated fatty acids modify phosphoenolpyruvate carboxykinase activity and lipid synthesis from glucose in adipose tissue of rats fed a high-sucrose diet.

Long-chain polyunsaturated n-3 fatty acids (n-3 LCPUFAs) have hypolipidemic effects and modulate intermediary metabolism to prevent or reverse insulin resistance in a way that is not completely elucidated. Here, effects of these fatty acids on the lipid profile, phosphoenolpyruvate carboxykinase (PEPCK) activity, lipid synthesis from glucose in epididymal adipose tissue (Ep-AT) and liver were investigated. Male rats were fed a high-sucrose diet (SU diet), containing either sunflower oil or a mixture of sunflower and fish oil (SU-FO diet), and the control group was fed a standard diet. After 13 weeks, liver, adipose tissue and blood were harvested and analysed. The dietary n-3 LCPUFAs prevented sucrose-induced increase in adiposity and serum free fat acids, serum and hepatic triacylglycerol and insulin levels. Furthermore, these n-3 LCPUFAs decreased lipid synthesis from glucose and increased PEPCK activity in the Ep-AT of rats fed the SU-FO diet compared to those fed the SU diet, besides reducing lipid synthesis from glucose in hepatic tissue. Thus, the inclusion of n-3 LCPUFAs in the diet may be beneficial for the prevention or attenuation of dyslipidemia and insulin resistance, and for reducing the risk of related chronic diseases.

Homocysteine induces energy imbalance in rat skeletal muscle: is creatine a protector?

Homocystinuria is a neurometabolic disease caused by a severe deficiency of cystathionine beta-synthase activity, resulting in severe hyperhomocysteinemia. Affected patients present several symptoms including a variable degree of motor dysfunction. In this study, we investigated the effect of chronic hyperhomocysteinemia on the cell viability of the mitochondrion, as well as on some parameters of energy metabolism, such as glucose oxidation and activities of pyruvate kinase, citrate synthase, isocitrate dehydrogenase, malate dehydrogenase, respiratory chain complexes and creatine kinase in gastrocnemius rat skeletal muscle. We also evaluated the effect of creatine on biochemical alterations elicited by hyperhomocysteinemia. Wistar rats received daily subcutaneous injections of homocysteine (0.3-0.6 µmol/g body weight) and/or creatine (50 mg/kg body weight) from the 6th to the 28th days of age. The animals were decapitated 12 h after the last injection. Homocysteine decreased the cell viability of the mitochondrion and the activities of pyruvate kinase and creatine kinase. Succinate dehydrogenase was increased other evaluated parameters were not changed by this amino acid. Creatine, when combined with homocysteine, prevented or caused a synergistic effect on some changes provoked by this amino acid. Creatine per se or creatine plus homocysteine altered glucose oxidation. These findings provide insights into the mechanisms by which homocysteine exerts its effects on skeletal muscle function, more studies are needed to elucidate them. Although creatine prevents some alterations caused by homocysteine, it should be used with caution, mainly in healthy individuals because it could change the homeostasis of normal physiological functions.

A Mechanism of Action of Metformin in the Brain: Prevention of Methylglyoxal-Induced Glutamatergic Impairment in Acute Hippocampal Slices.

Metformin, a biguanide compound (N-1,1-dimethylbiguanide), is widely prescribed for diabetes mellitus type 2 (T2D) treatment. It also presents a plethora of properties, such as anti-oxidant, anti-inflammatory, anti-apoptosis, anti-tumorigenic, and anti-AGE formation activity. However, the precise mechanism of action of metformin in the central nervous system (CNS) needs to be clarified. Herein, we investigated the neuroprotective role of metformin in acute hippocampal slices exposed to methylglyoxal (MG), a highly reactive dicarbonyl compound and a key molecule in T2D developmental pathophysiology. Metformin protected acute hippocampal slices from MG-induced glutamatergic neurotoxicity and neuroinflammation by reducing IL-1ß synthesis and secretion and RAGE protein expression. The drug also improved astrocyte function, particularly with regard to the glutamatergic system, increasing glutamate uptake. Moreover, we observed a direct effect of metformin on glutamate transporters, where the compound prevented glycation, by facilitating enzymatic phosphorylation close to Lys residues, suggesting a new neuroprotective role of metformin via PKC ζ in preventing dysfunction in glutamatergic system induced by MG. Proposed neuroprotection role of metformin in acute hippocampal slices against impairment in glutamatergic system induced in a model of methylglyoxal glycotoxicity. Metformin reversed methylglyoxal (MG)-induced neuroinflammation by reducing pro-inflammatory IL-1ß synthesis and secretion and RAGE protein expression. Metformin did not alter the effect of MG on S100B secretion (1). Both MG and metformin also influenced astrocyte function in hippocampal slices. Metformin did not reverse the elevation in GLO1 activity induced by glycotoxicity; however, it abrogated the high GSH level and the expression of the co-factor of GLO1 (2). Both treatments per se changed bioenergetic metabolism and increased glucose uptake, extracellular lactate content, and pyruvate kinase (PK) activity. The increment in glucose uptake and lactate levels ceased during the co-incubation of MG with metformin. Metformin reversed the elevation of hexokinase activity by MG (3). We suggest a new role of metformin in the glutamate system, whereby it protects the hippocampus against the derangements of the glutamatergic system induced by MG, possibly by phosphorylation via PKC ζ (4). The neuroprotective action of metformin may be mediated by the phosphorylation of specific amino acid residues (Lysine) of the glutamate transporters (GLAST and GLT-1), since metformin activated the PKC ζ signaling and promoted cascades of phosphorylation in p38 MAPK and Akt proteins. The transporter protein phosphorylation prevented the Lys-glycation and the impairment of glutamate uptake induced by MG (5).

Effects of physical training on functional, clinical, morphological, behavioural and psychosocial outcomes in post-COVID-19 infection: COVID-19 and REhabilitation study (CORE-study)-a study protocol for a randomised controlled clinical trial.

BACKGROUND: The COVID-19 pandemic remains ongoing, with a significant number of survivors who have experienced moderate to severe clinical conditions and who have suffered losses of great magnitude, especially in functional capacity, triggering limitations to daily autonomy and quality of life. Among the possibilities of intervention for disease rehabilitation, physical exercise training stands out, which can benefit several health outcomes and favours the adoption of healthier behaviours. Therefore, the aim of the study will be to analyse the effects of physical training on the functional, clinical, morphological, behavioural and psychosocial status in adults and the elderly following COVID-19 infection. METHODS: A randomised controlled clinical trial is to be conducted in parallel, with the experimental group undergoing an intervention involving a multicomponent physical rehabilitation programme, carried out at the Sports Center in partnership with the Academic Hospital of the Federal University of Santa Catarina, in Florianópolis, Brazil. Participants will be adults and the elderly, of both sexes, in a post-COVID-19-infection state, who were hospitalised during the infection. The intervention will have a total duration of 24 weeks and will include a multicomponent physical training programme, which will have gradual progression in frequency, duration and intensity over time. Regarding the outcomes, before, at the 12th and after 24 weeks of intervention, functional (primary outcome = functional index of aerobic capacity), clinical, morphological, behavioural and psychosocial outcomes will be assessed. DISCUSSION: This study will contribute to a greater understanding of the safety, adherence and benefits of physical training in the rehabilitation of post-COVID-19 patients. The results of this study will be disseminated through presentations at congresses, workshops, peer-reviewed publications and local and international conferences, especially with a view to proposing a post-COVID-19 rehabilitation care protocol. TRIAL REGISTRATION: ReBEC, RBR-10y6jhrs . Registered on 22 February 2022. 2015.

Methylglyoxal alters glucose metabolism and increases AGEs content in C6 glioma cells.

Methylglyoxal is a dicarbonyl compound that is physiologically produced by enzymatic and non-enzymatic reactions. It can lead to cytotoxicity, which is mainly related to Advanced Glycation End Products (AGEs) formation. Methylglyoxal and AGEs are involved in the pathogenesis of Neurodegenerative Diseases (ND) and, in these situations, can cause the impairment of energetic metabolism. Astroglial cells play critical roles in brain metabolism and the appropriate functioning of astrocytes is essential for the survival and function of neurons. However, there are only a few studies evaluating the effect of methylglyoxal on astroglial cells. The aim of this study was to evaluate the effect of methylglyoxal exposure, over short (1 and 3 h) and long term (24 h) periods, on glucose, glycine and lactate metabolism in C6 glioma cells, as well as investigate the glyoxalase system and AGEs formation. Glucose uptake and glucose oxidation to CO(2) increased in 1 h and the conversion of glucose to lipids increased at 3 h. In addition, glycine oxidation to CO(2) and conversion of glycine to lipids increased at 1 h, whereas the incorporation of glycine in proteins decreased at 1 and 3 h. Methylglyoxal decreased glyoxalase I and II activities and increased AGEs content within 24 h. Lactate oxidation and lactate levels were not modified by methylglyoxal exposure. These data provide evidence that methylglyoxal may impair glucose metabolism and can affect glyoxalase activity. In periods of increased methylglyoxal exposure, such alterations could be exacerbated, leading to further increases in intracellular methylglyoxal and AGEs, and therefore triggering and/or worsening ND.

Fruit-Derived Anthocyanins: Effects on Cycling-Induced Responses and Cycling Performance.

Previous evidence has shown that the consumption of fruit-derived anthocyanins may have exercise benefits. This review aimed to summarize the effects of fruit-derived anthocyanins on cycling-induced responses and cycling performance. Medline, Science Direct, Cochrane Library, and SPORTDiscus online databases were searched. Nineteen articles met the inclusion criteria. The fruit-derived anthocyanins used in these studies were from cherry (n = 6), blackcurrant (n = 8), pomegranate (n = 2), açai (n = 1), and juçara fruit (n = 2), and were offered in juice, pulp, powder, freeze-dried powder, and extract form. The supplementation time ranged from acute consumption to 20 days, and the amount of anthocyanins administered in the studies ranged from 18 to 552 mg/day. The studies addressed effects on oxidative stress (n = 5), inflammation (n = 4), muscle damage (n = 3), fatigue (n = 2), nitric oxide biomarkers (n = 2), vascular function (n = 2), muscle oxygenation (n = 2), performance (n = 14), substrate oxidation (n = 6), and cardiometabolic markers (n = 3). The potential ergogenic effect of anthocyanin supplementation on cycling-induced responses seems to be related to lower oxidative stress, inflammation, muscle damage, and fatigue, and increased production of nitric oxide, with subsequent improvements in vascular function and muscle oxygenation leading to improved performance. In addition, the observed increase in fat oxidation can direct nutritional strategies to change the use of substrate and improve performance.

Nine weeks of combined training improve functional and morphological outcomes in trained older people with cardiometabolic risk factors.

BACKGROUND: The study is characterized as a single group experiment, with the aim of verifying the responses of functional capacity and body composition, after a combined training program with undulating periodization, of low cost and easy applicability, in volunteers with cardiovascular risk factors. METHODS: Experimental study carried out with individuals of both sexes, with cardiometabolic risk factors, members of a Cardiorespiratory Rehabilitation Program (PROCOR) of the Federal University of Santa Catarina (UFSC). A combined physical training program (aerobic and strength) with load training progression was used, performed at a frequency of three weekly sessions, on alternate days, for nine weeks and using shin guards, elastic bands or just body weight. Functional capacity, anthropometric profile and body composition of individuals were evaluated before and after the intervention. The comparison of data before and after the intervention period was performed using the Student's t-test for paired samples and the Wilcoxon test. RESULTS: Improvements statistically significant were observed in the tests related to functional capacity, "Sit and Stand", "8-foot-up-and-go" at usual and maximum speeds and "March", along with a decrease in anthropometric measurements of hip circumference, body fat percentage, waist-to-hip ratio, and fat mass in the android region. In addition, the program was well-tolerated with a low rate of sample losses. CONCLUSION: The results of this study suggest that only 9 weeks of combined training at low cost and easy applicability is able to promote improvement in parameters related to functional capacity, anthropometric profile, and body composition of trained older people with cardiovascular risk factors.

Vitamin D is associated with body composition and fat intake, but not with cardiometabolic parameters in adults with obesity.

Adults with obesity are at higher risk for developing hypovitaminosis D. Some studies suggest that reduced levels of serum 25-hydroxyvitamin D (25(OH)D) may also be related to disorders in cardiometabolic parameters. However, because of the association between 25(OH)D and obesity, we hypothesized that body composition can be a confounding factor in the association of 25(OH)D with cardiometabolic parameters, and that 25(OH)D is inversely associated with body composition and cardiometabolic parameters and directly associated with fat intake. The aim of this study was to analyze the associations between 25(OH)D with body composition, fat intake, and cardiometabolic parameters in adults with obesity. This cross-sectional study consisted of 52 adults with obesity (61.53% female; 37.50 ± 6.88 years; body mass index [BMI]: 33.60 ± 2.89 kg/m2). Cardiometabolic parameters (fasting blood glucose, insulin resistance index, C-reactive protein, blood pressure, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and cholesterol), body mass, BMI, waist circumference, body fat percentage, and fat intake were evaluated. Body mass was negatively associated with 25(OH)D (ß = -0.108; P = .048; and R² = 0.090) and BMI (ß = -0.621; P = .031; and R² = 0.103), both adjusted for fat intake. 25(OH)D was positively associated with fat intake (ß = 0.129; P = .045 and R² = 0.078) adjusted for sex, age, and skin color. Cardiometabolic parameters were not associated with 25(OH)D, even after adjusted by body composition variables. However, the high prevalence of hypovitaminosis D (75%) and the negative association between 25(OH)D and body composition reinforce the importance of analyzing and monitoring vitamin D status in this population.

Inflammatory cytokines and alcohol use disorder: systematic review and meta-analysis.

OBJECTIVE: To assess differences in blood inflammatory cytokines between people with alcohol use disorder (AUD) and healthy controls (HC). METHODS: Searches were performed from inception through April 14, 2021. Meta-analyses with random-effects models were used to calculate the standardized mean difference ([SMD], 95%CI), and potential sources of heterogeneity were explored trough meta-regressions and subgroup analysis. RESULTS: The meta-analysis included 23 studies on the following 14 cytokines: tumor necrosis factor (TNF)-a, IL-1, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-13, IL15, interferon (IFN)-g and sCD14. There were significantly higher concentrations of IL-6 (n=462 AUD and 408 HC; SMD = 0.523; 95%CI 0.136-0.909; p = 0.008) in AUD than HC. No significant differences were found in the other 13 cytokines. CONCLUSION: We found that IL-6 levels were significantly higher in individuals with AUD than HC and that other cytokines were not altered. This can be explained by the small number of studies, their methodological heterogeneity, and confounding factors (active use, abstinence, quantity, and physical or psychiatric illnesses, for example). Despite a great deal of evidence about alcohol and inflammatory diseases, studies assessing the role of neuroimmune signaling in the development and severity of AUD are still lacking.

Acute Methylglyoxal-Induced Damage in Blood-Brain Barrier and Hippocampal Tissue.

Methylglyoxal (MG) is a reactive dicarbonyl compound formed mostly via the glycolytic pathway. Elevated blood glucose levels can cause MG accumulation in plasma and cerebrospinal fluid in patients with diabetes mellitus and Alzheimer's disease. Under these disease conditions, the high reactivity of MG leads to modification of proteins and other biomolecules, generating advanced glycation end products (AGEs), which are considered mediators in neurodegenerative diseases. We investigated the integrity of the blood-brain barrier (BBB) and astrocyte response in the hippocampus to acute insult induced by MG when it was intracerebroventricularly administered to rats. Seventy-two hours later, BBB integrity was lost, as assessed by the entry of Evans dye into the brain tissue and albumin in the cerebrospinal fluid, and a decrease in aquaporin-4 and connexin-43 in the hippocampal tissue. MG did not induce changes in the hippocampal contents of RAGE in this short interval, but decreased the expression of S100B, an astrocyte-secreted protein that binds RAGE. The expression of two important transcription factors of the antioxidant response, NF-κB and Nrf2, was unchanged. However, hemeoxigenase-1 was upregulated in the MG-treated group. These data corroborate the idea that hippocampal cells are targets of MG toxicity and that BBB dysfunction and specific glial alterations induced by this compound may contribute to the behavioral and cognitive alterations observed in these animals.

Metabolically unhealthy and overweight phenotypes are associated with increased levels of inflammatory cytokines: a population-based study.

OBJECTIVE: The aim of this study was to determine the association between cytokine levels in metabolic phenotypes. Our hypothesis was that an unhealthy metabolic profile is associated to higher levels of proinflammatory cytokines. METHODS: The study sample was composed of 743 Brazilian adults classified in four phenotypes: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight (MHOW), and metabolically unhealthy overweight (MUOW). Sociodemographic, anthropometric, clinical, and biochemical parameters were collected. Six different cytokines were analyzed from blood samples using the CBA Human Inflammatory cytokines kit and the values divided in quartiles for analysis. Logistic regression models were constructed to assess the association between metabolic phenotypes and cytokines concentrations, adjusted for potential confounders and P < 0.05 was used. RESULTS: The MUOW phenotype showed a higher risk for increased levels of all cytokines analyzed compared with the reference group (MHNW). CONCLUSIONS: These results indicated that excess weight and altered metabolic profile are related to inflammation, especially when both conditions are associated, possibly linked to visceral adiposity. Therefore, the categorization of metabolic phenotypes in populations is an important factor for prevention of chronic diseases, as inflammation is associated with cardiovascular risk and obesity is not the only influencing factor.