Moderate chronic sleep perturbation impairs glucose and lipid homeostasis in rats.

STUDY OBJECTIVES: Sleep deprivation is a potential risk factor for metabolic diseases, including obesity and type 2 diabetes. We evaluated the impacts of moderate chronic sleep deprivation on glucose and lipid homeostasis in adult rats. METHODS: Wistar rats (both sexes) were sleep-perturbed daily for 2 hours at the early (06:00-08:00) and the late light cycle (16:00-18:00) five days a week (except weekends) for 4 weeks. RESULTS: Sleep perturbation (SP) resulted in reduced body weight gain in both sexes, associated with altered food intake and reduced adiposity. SP did not alter the short- or long-term memories or cause anxiogenic behavior. No major changes were observed in the plasma insulin, leptin, triacylglycerol, non-esterified fatty acids, and blood glucose upon SP. After SP, females exhibited a transitory glucose intolerance, while males became glucose intolerant at the end of the experimental period. Male rats also developed higher insulin sensitivity at the end of the SP protocol. Morphometric analyses revealed no changes in hepatic glycogen deposition, pancreatic islet mass, islet-cell distribution, or adrenal cortex thickness in SP rats from both sexes, except for lower adipocyte size compared with controls. We did not find homogeneous changes in the relative expression of circadian and metabolic genes in muscle or hepatic tissues from the SP rats. CONCLUSIONS: Moderate chronic SP reduces visceral adiposity and causes glucose intolerance with a more pronounced impact on male rats, reinforcing the metabolic risks of exposure to sleep disturbances.

A systematic review and meta-analysis demonstrating Klotho as an emerging exerkine.

Klotho is an anti-aging protein with several therapeutic roles in the pathophysiology of different organs, such as the skeletal muscle and kidneys. Available evidence suggests that exercise increases Klotho levels, regardless of the condition or intervention, shedding some light on this anti-aging protein as an emergent and promising exerkine. Development of a systematic review and meta-analysis in order to verify the role of different exercise training protocols on the levels of circulating soluble Klotho (S-Klotho) protein. A systematic search of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE through PubMed, EMBASE, CINAHL, CT.gov, and PEDro. Randomized and quasi-randomized controlled trials that investigated effects of exercise training on S-Klotho levels. We included 12 reports in the analysis, comprising 621 participants with age ranging from 30 to 65 years old. Klotho concentration increased significantly after chronic exercise training (minimum of 12 weeks) (Hedge' g [95%CI] 1.3 [0.69-1.90]; P < 0.0001). Moreover, exercise training increases S-Klotho values regardless of the health condition of the individual or the exercise intervention, with the exception of combined aerobic + resistance training. Furthermore, protocol duration and volume seem to influence S-Klotho concentration, since the effect of the meta-analysis changes when subgrouping these variables. Altogether, circulating S-Klotho protein is altered after chronic exercise training and it might be considered an exerkine. However, this effect may be influenced by different training configurations, including protocol duration, volume, and intensity.

Impact of combined long-term fructose and prednisolone intake on glucose and lipid homeostasis in rats: benefits of intake interruption or fish oil administration.

We investigated whether combined long-term fructose and prednisolone intake would be more detrimental to the glucose homeostasis than if ingested separately. We also evaluated whether fish oil administration or interruption of treatments has any positive impact. For this, male adult Wistar rats ingested fructose (20%) (F) or prednisolone (12.5 µg/mL) (P) or both (FP) through drinking water for 12 weeks. A separate group of fructose and prednisolone-treated rats received fish oil treatment (1 g/kg) in the last 6 weeks. In another group, the treatment with fructose and prednisolone was interrupted after 12 weeks, and the animals were followed for more 12 weeks. Control groups ran in parallel (C). The F group had higher plasma TG (+42%) and visceral adiposity (+63%), whereas the P group had lower insulin sensitivity (-33%) and higher insulinemia (+200%). Only the the FP group developed these alterations combined with higher circulating uric acid (+126%), hepatic triacylglycerol content (+16.2-fold), lipid peroxidation (+173%) and lower catalase activity (-32%) that were associated with lower protein kinase B content and AMP-activated protein kinase (AMPK) phosphorylation in the liver, lower AMPK phosphorylation in the adipose tissue and higher beta-cell mass. Fish oil ingestion attenuated the elevation in circulating triacylglycerol and uric acid values, while the interruption of sugar and glucocorticoid intake reverted almost all modified parameters. In conclusion, long-term intake of fructose and prednisolone by male rats are more detrimental to glucose and lipid homeostasis than if ingested separately and the benefits of treatment interruption are broader than fish oil treatment.

Fructose Intake Impairs Cortical Antioxidant Defenses Allied to Hyperlocomotion in Middle-Aged C57BL/6 Female Mice.

Recent evidence suggests that young rodents submitted to high fructose (FRU) diet develop metabolic, and cognitive dysfunctions. However, it remains unclear whether these detrimental effects of FRU intake can also be observed in middle-aged mice. Nine months-old C57BL/6 female mice were fed with water (Control) or 10% FRU in drinking water during 12 weeks. After that, metabolic, and neurochemical alterations were evaluated, focusing on neurotransmitters, and antioxidant defenses. Behavioral parameters related to motor activity, memory, anxiety, and depression were also evaluated. Mice consuming FRU diet displayed increased water, and caloric intake, resulting in weight gain, which was partially compensated due to decreased food pellet intake. FRU fed animals displayed increased plasma glucose, and cholesterol levels, which was not observed in overnight-fasted animals. Superoxide dismutase (SOD), and catalase (CAT) activities were markedly decreased in the prefrontal cortex of animals receiving FRU diet, while glutathione peroxidase (GPx) slightly increased. Liver (lower GPx), striatum (higher SOD and lower CAT), and hippocampus (no changes) were less impacted. No changes were observed in glutathione reductase, and thioredoxin reductase activities, two ancillary enzymes for peroxide detoxification. FRU intake did not alter serotonin, dopamine, and norepinephrine levels in the hippocampus, prefrontal cortex, and striatum. No significant alterations were observed in working, and short-term spatial memory; and in anxiety- and depressive-like behaviors in animals treated with FRU. Increased locomotor activity was observed in FRU-fed middle-aged mice, as evaluated in the open field, elevated plus-maze, Y maze, and object location tasks. Overall, these results demonstrate that high FRU consumption can disturb antioxidant defenses, and increase locomotor activity in middle-aged mice, open the opportunity for further studies to address the underlying mechanisms related to these findings.

Frequency of gene ace i polymorphism i-d in athletes of different sports / Frequência do polimorfismo i-d do gene eca i em atletas de diferentes esportes / Frecuencia del polimorfismo i-d del gen eca i en atletas de diferentes deportes

ABSTRACT Introduction: The angiotensin-converting enzyme I-D (ACE) polymorphism gene is one of the most widely investigated genetic variations in sports science. Apparently, allele I is related to endurance sports, while allele D is related to power-strength activities. Nevertheless, studies have presented controversial results when it comes as to its occurrence in a variety of sports. Objective: This study aims to evaluate the frequency of gene ACE polymorphism I-D in professional athletes of collective or individual sports. Methods: Five mL blood were collected from 189 subjects divided into two groups: athletes (AG, n=127, wrestling, taekwondo, soccer, futsal and handball) and non-athletes (NAG, n=62). The athletes group was subdivided by group modalities, into: collective and individual. Both groups were further subdivided into male and female. Thus, we have the groups FAC= collective female, FAI= individual female, MAC= collective male, and MAI= individual male. The statistical analysis was carried out by frequency test, and the Hardy- Weinberg equilibrium by the x² test. Results: The results for the AG group indicated the following frequencies: DD=7%, ID=44% and II=49%. Allele frequency: D=29% and I=71%. For the NAG, the results were: DD=6.5%, ID=45.2% and II=48%. Allele frequency: D=29% and I=71%. The AG genotypic and allele frequencies did not differ statistically from those of the NAG (p= 0.982 and p= 0.984, respectively). However, we noticed that the genotypes II and ID frequencies were significantly higher than those of the DD. Conclusion: It can be concluded that the genotypic and allelic I-D frequencies of the ACE gene do not seem to influence performance in either group or individual sports. ACTN3 genotype frequencies did not vary significantly between male and female control subjects, and overall, there was no significant deviation from Hardy-Weinberg (H-W) equilibrium. Level of evidence I; Diagnostic studies-Investigating diagnostic test.

RESUMO Introdução: O polimorfismo I-D do gene da enzima conversora da angiotensina (ECA) é uma das variações genéticas mais amplamente investigadas na ciência do esporte. Aparentemente, o alelo I está relacionado aos esportes de resistência e o alelo D às atividades de força. Entretanto, os estudos têm apresentado resultados controversos quanto a sua ocorrência em diversos esportes. Objetivo: O presente estudo pretende avaliar a frequência do polimorfismo I-D do gene da ECA em atletas profissionais de esportes coletivos ou individuais. Métodos: Cinco mL de sangue foram coletados de 189 indivíduos divididos em dois grupos: atletas (GA, n=127, praticantes de luta livre, taekwondo, futebol, futsal ou handebol) e não atletas (GNA, n=62). O grupo de atletas foi subdividido de acordo com a modalidade: coletiva e individual. Ambos os grupos foram também subdivididos em masculino e feminino. Portanto, temos os grupos FAC = feminino coletivo, FAI = feminino individual, MAC = masculino coletivo, MAI = masculino individual. A análise estatística foi realizada através do teste de frequência e o equilíbrio de Hardy-Weinberg pelo teste x². Resultados: Os resultados para o GA indicaram as seguintes frequências: DD=7%, ID=44% e II=49%. Frequência alélica: D=29% e I=71%. Para o GNA, os resultados foram: DD=6,5%, ID=45,2% e II=48%. Frequência alélica: D=29% e I=71%. As frequências genotípicas e alélicas do GA não se diferiram estatisticamente daquelas do GNA (p= 0,982 e p= 0,984, respectivamente). Entretanto, notamos que as frequências dos genótipos II e ID se apresentaram significativamente maiores do que aquelas do DD. Conclusão: Pode-se concluir que as frequências I-D genotípicas e alélicas do gene da ECA não pareceram influenciar o desempenho tanto nos esportes individuais como coletivos. As frequências do genótipo ACTN3 não variaram significativamente entre os indivíduos de controle de ambos os sexos, e, no geral, não houve um desvio significativo do equilíbrio de Hardy-Weinberg (H-W). Nível de evidência I; Estudos diagnósticos-Investigação de um exame para diagnóstico.

RESUMEN Introducción: El polimorfismo I-D del gen de la enzima convertidora de la angiotensina (ECA) es una de las variaciones genéticas más ampliamente investigadas en la ciencia del deporte. Aparentemente, el alelo I está relacionado a los deportes de resistencia y el alelo D a las actividades de fuerza. Entretanto, los estudios han presentado resultados controvertidos cuanto a su ocurrencia en diversos deportes. Objetivo: El presente estudio pretende evaluar la frecuencia del polimorfismo I-D del gen de la ECA en atletas profesionales de deportes colectivos o individuales. Métodos: Cinco mL de sangre fueron recolectados de 189 individuos divididos en dos grupos: atletas (GA, n=127 practicantes de lucha libre, taekwondo, fútbol, futsal y hándbol) y no atletas (GNA, n=62). El grupo de atletas fue subdividido de acuerdo con la modalidad: colectiva e individual. Ambos grupos fueron también subdivididos en masculino y femenino: Por lo tanto, tenemos los grupos FAC= colectivo femenino, FAI= femenino individual, MAC= masculino colectivo, MAI= masculino individual. El análisis estadístico fue realizado a través del test de frecuencia, y el equilibrio de Hardy-Weinberg por el test x². Resultados: Los resultados de GA indicaran las siguientes frecuencias: DD=7%, ID=44% y II=49%. Frecuencia alélica: D=29% e I=71%. Para el GNA, los resultados fueron: DD=6,5%, ID=45,2% y II=48%. Frecuencia alélica: D=29% e I=71%. Las frecuencias genotípicas y alélicas del GA no difirieron estadísticamente de las del GNA (p=0,982 y p=0,984, respectivamente). Entretanto, notamos que las frecuencias de los genotipos II e ID se presentaron significativamente mayores que aquellas del DD. Conclusión: Se puede concluir que las frecuencias I-D genotípicas y alélicas del gen de la ECA no parecieron influenciar el desempeño tanto en los deportes individuales como colectivos. Las frecuencias del genotipo ACTN3 no variaron significativamente entre los individuos de control de ambos sexos y, en general, no hubo desvío significativo del equilibrio de Hardy-Weinberg (H-W). Nivel de evidencia I; Estudios diagnósticos-Investigación de un examen para diagnóstico.

Impact of glucocorticoid treatment before pregnancy on glucose homeostasis of offspring exposed to glucocorticoid in adult life.

AIMS: To explore the impact of GC administration periconceptionally on the glucose metabolism of adult offspring (male and female) and whether this periconception exposure might influence the metabolic outcomes when the offspring are also treated with dexamethasone in adult life. MATERIALS AND METHODS: Rats received a daily injection of dexamethasone (1 mg/kg, body mass) or saline solution (1 mL/kg body mass) for 7 consecutive days prior became pregnant. Male and female offspring had glucose homeostasis assessed at 3- and 6-month-old and after dexamethasone treatment (1 mg/kg, body mass) or vehicle for 5 consecutive days. Then, murinometric, functional, biochemical, and histomorphometric analyses were performed. KEY FINDINGS: Male and female offspring born from rats treated with GC prior to becoming pregnant had none of the murinometric and metabolic outcomes (i.e., body mass, food intake, blood glucose, plasma triacylglycerol, and glucose tolerance) changed up to 6-month-old. None of the expected diabetogenic effects caused by dexamethasone treatment at 6-month of age (i.e., elevation in fasting blood glucose, plasma insulin, triacylglycerol, and albumin, glucose intolerance, insulin insensitivity, augmentation in hepatic glycogen content, and increase in pancreatic islet mass) was observed in offspring born from rats treated with dexamethasone in the prepregnancy period. However, periconceptional exposure to GC predisposed the offspring of both sexes to a higher prevalence of augmented fed blood glucose values. SIGNIFICANCE: These results give validity for the use of GC as anti-inflammatory purposes in this critical periconceptional period, but highlight the importance to consider all parental habits when interpreting adult outcomes.

Fish oil decreases the severity of treatment-related adverse events in gastrointestinal cancer patients undergoing chemotherapy: A randomized, placebo-controlled, triple-blind clinical trial.

BACKGROUND AND AIMS: Due to its high peroxidizable characteristics, n-3 fatty acids, present in fish oil, could increase tumor cells sensitivity to conventional cancer treatment while non-neoplastic cells remain unaffected, this may lead to an increase in cancer treatment response with no increase on adverse effects. The aim of this study was to evaluate anti-cancer treatment response, performance status and adverse events in gastrointestinal cancer patients supplemented with fish oil. Oxidative stress parameters were investigated in blood non-neoplastic cells as an indicator of cytotoxicity. METHODS: This is a randomized, triple-blind, placebo-controlled clinical trial. Fish oil group (FOG) received two capsules of fish oil containing 1.55 g of EPA + DHA a day for nine weeks, placebo group (PG) received two capsules containing olive oil. Baseline was set right before the administration of the first chemotherapy, oxidative stress parameters, adverse events presence and grading and performance status were assessed at baseline and after nine weeks of supplementation. Tumor markers, response to treatment and survival were evaluated at baseline and after one year of study inclusion. RESULTS: 76 patients were considered eligible, 56 were randomized, and 51 remained for analysis. After nine weeks, although there were no differences between groups for treatment response and presence of adverse events, PG patients were graded with more severe diarrhea than FOG patients (p = 0.03) and with higher (worse) performance status score (p = 0.02). No differences in lipid peroxidation and activity of antioxidant enzymes were observed between groups. CONCLUSIONS: Fish oil may lead to a better performance status for gastrointestinal cancer patients undergoing chemotherapy while does not seem to increase treatment-related toxicity. Registered under ClinicalTrials.gov Identifier no. NCT02699047, www.clinicaltrials.gov.

Effect of mate tea (Ilex paraguariensis) on the expression of the leukocyte NADPH oxidase subunit p47phox and on circulating inflammatory cytokines in healthy men: a pilot study.

Increased superoxide production by phagocytic NADPH oxidase has been associated with inflammatory conditions. Growing evidences suggest that dietary polyphenols may modulate the expression of NADPH oxidase subunits. Herein, we examined whether soluble mate tea (SMT) consumption - a polyphenol-rich beverage - affects the expression of the leukocyte NADPH oxidase protein p47phox and/or circulating biomarkers of inflammation and antioxidant biomarkers in humans. In a two-phase study, nine men were requested to drink water (control) for 8 d and then follow a second 8-d period drinking SMT. Blood samples were analysed for p47phox protein in CD16+/CD14- cells, interleukin (IL)-1ß (IL-1ß), tumour necrosis factor-alpha (TNF-α), IL-6, total phenols, and reduced and oxidised glutathione (GSH and GSSG, respectively) after each study phase. After SMT intake, CD16+/CD14- cells' p47phox protein and serum TNF-α and IL-6 levels were significantly attenuated (P < .05) while plasma phenolic compounds and blood GSH:GSSG ratio were significantly enhanced (P < .05). Consumption of SMT favourably affected leukocytes' p47phox expression and inflammatory cytokine and antioxidants levels in peripheral blood, which may help decrease oxidative stress and low-grade inflammation.

Decrement in resting and insulin-stimulated soleus muscle mitochondrial respiration is an early event in diet-induced obesity in mice.

NEW FINDINGS: What is the central question of this study? What are the temporal responses of mitochondrial respiration and mitochondrial responsivity to insulin in soleus muscle fibres from mice during the development of obesity and insulin resistance? What is the main finding and its importance? Short- and long-term feeding with a high-fat diet markedly reduced soleus mitochondrial respiration and mitochondrial responsivity to insulin before any change in glycogen synthesis. Muscle glycogen synthesis and whole-body insulin resistance were present after 14 and 28 days, respectively. Our findings highlight the plasticity of mitochondria during the development of obesity and insulin resistance. ABSTRACT: Recently, significant attention has been given to the role of muscle mitochondrial function in the development of insulin resistance associated with obesity. Our aim was to investigate temporal alterations in mitochondrial respiration, H2 O2 emission and mitochondrial responsivity to insulin in permeabilized skeletal muscle fibres during the development of obesity in mice. Male Swiss mice (5-6 weeks old) were fed with a high-fat diet (60% calories from fat) or standard diet for 7, 14 or 28 days to induce obesity and insulin resistance. Diet-induced obese (DIO) mice presented with reduced glucose tolerance and hyperinsulinaemia after 7 days of high-fat diet. After 14 days, the expected increase in muscle glycogen content after systemic injection of glucose and insulin was not observed in DIO mice. At 28 days, blood glucose decay after insulin injection was significantly impaired. Complex I (pyruvate + malate) and II (succinate)-linked respiration and oxidative phosphorylation (ADP) were decreased after 7 days of high-fat diet and remained low in DIO mice after 14 and 28 days of treatment. Moreover, mitochondria from DIO mice were incapable of increasing respiratory coupling and ADP responsivity after insulin stimulation in all observed periods. Markers of mitochondrial content were reduced only after 28 days of treatment. The mitochondrial H2 O2 emission profile varied during the time course of DIO, with a reduction of H2 O2 emission in the early stages of DIO and an increased emission after 28 days of treatment. Our data demonstrate that DIO promotes transitory alterations in mitochondrial physiology during the early and late stages of insulin resistance related to obesity.

Effects of mate tea consumption on muscle strength and oxidative stress markers after eccentric exercise.

Dietary phytochemical supplementation may improve muscle recovery from exercise. In this study, we investigated the effect of mate tea (MT) consumption - a phenol-rich beverage - on muscle strength and oxidative stress biomarkers after eccentric exercise. In a randomised, cross-over design, twelve men were assigned to drink either MT or water (control; CON) for 11 d. On the 8th day, subjects performed three sets of twenty maximal eccentric elbow flexion exercises. Maximal isometric elbow flexion force was measured before and at 0, 24, 48 and 72 h after exercise. Blood samples were obtained before and at 24, 48 and 72 h after exercise and analysed for total phenolics, GSH, GSSG, GSH:GSSG ratio and lipid hydroperoxides (LOOH). After eccentric exercise, muscle strength was significantly reduced over time, regardless of treatments. However, MT improved the rate of strength recovery by 8·6 % on the 1st day after exercise (P<0·05). Plasma concentration of total phenolic compounds was higher in MT than in CON at all time points (P<0·05) but decreased significantly at 72 h after exercise in both trials (P<0·05). Blood levels of GSH were significantly decreased at 48 and 72 h after exercise in CON (P<0·05) but did not change over time in MT. No significant changes were observed for GSSG, GSH:GSSG ratio and LOOH levels. MT intake did not influence muscle strength at all time points assessed but hastened the strength recovery over 24 h after exercise. MT also favoured the concentration of blood antioxidant compounds.