Determination of the anti-inflammatory and cytoprotective effects of l-glutamine and l-alanine, or dipeptide, supplementation in rats submitted to resistance exercise.

We evaluated the effects of chronic oral supplementation with l-glutamine and l-alanine in their free form or as the dipeptide l-alanyl-l-glutamine (DIP) on muscle damage, inflammation and cytoprotection, in rats submitted to progressive resistance exercise (RE). Wistar rats (n 8/group) were submitted to 8-week RE, which consisted of climbing a ladder with progressive loads. In the final 21 d before euthanasia, supplements were delivered in a 4 % solution in drinking water. Glutamine, creatine kinase (CK), lactate dehydrogenase (LDH), TNF-α, specific IL (IL-1ß, IL-6 and IL-10) and monocyte chemoattractant protein-1 (MCP-1) levels were evaluated in plasma. The concentrations of glutamine, TNF-α, IL-6 and IL-10, as well as NF-κB activation, were determined in extensor digitorum longus (EDL) skeletal muscle. HSP70 level was assayed in EDL and peripheral blood mononuclear cells (PBMC). RE reduced glutamine concentration in plasma and EDL (P<0·05 v. sedentary group). However, l-glutamine supplements (l-alanine plus l-glutamine (GLN+ALA) and DIP groups) restored glutamine levels in plasma (by 40 and 58 %, respectively) and muscle (by 93 and 105 %, respectively). GLN+ALA and DIP groups also exhibited increased level of HSP70 in EDL and PBMC, consistent with the reduction of NF-κB p65 activation and cytokines in EDL. Muscle protection was also indicated by attenuation in plasma levels of CK, LDH, TNF-α and IL-1ß, as well as an increase in IL-6, IL-10 and MCP-1. Our study demonstrates that chronic oral l-glutamine treatment (given with l-alanine or as dipeptide) following progressive RE induces cyprotective effects mediated by HSP70-associated responses to muscle damage and inflammation.

Effects of Glutamine and Alanine Supplementation on Adiposity, Plasma Lipid Profile, and Adipokines of Rats Submitted to Resistance Training.

Glutamine and alanine are lipogenic and could prevent the effects of resistance training (RT) in reducing adiposity and modulating lipid profile. Thus, we aimed to investigate the effects of RT and glutamine and alanine supplementation, in their free or conjugated form, on relative epididymal adipose tissue (EAT) and brown adipose tissue (BAT) weight, plasma lipid profile, and adipokines in EAT. Thirty Wistar rats, aged two months, were distributed into five groups: control (CTRL), trained (TRN), trained and supplemented with alanine (ALA), glutamine and alanine in their free form (GLN+ALA), or L-alanyl-L-glutamine (DIP). Trained groups underwent a ladder-climbing exercise for eight weeks, with progressive load increase. Supplementations were offered in a solution with a concentration of 4% in the last 21 days of training. Food consumption and body weight gain were decreased in the TRN group compared with CTRL. RT also reduced relative EAT and BAT weight, while supplementations, especially with ALA, increased adipose tissue mass. RT reduced total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-c) (TRN vs. CTRL), whereas glutamine and alanine supplementation increased TC and LDL-c, impairing lipid profile modulation by physical exercise. RT did not affect the concentrations of adipokines in EAT, but DIP supplementation increased interleukin- (IL-) 6 and IL-10. In conclusion, RT reduced adiposity and modulated lipid profile, whereas glutamine and alanine supplementation increased adiposity and impaired lipid profile but increased the concentration of the anti-inflammatory cytokines IL-6 and IL-10 in EAT.

l-glutamine and l-alanine supplementation increase glutamine-glutathione axis and muscle HSP-27 in rats trained using a progressive high-intensity resistance exercise.

In this study we investigated the chronic effects of oral l-glutamine and l-alanine supplementation, either in their free or dipeptide form, on glutamine-glutathione (GLN-GSH) axis and cytoprotection mediated by HSP-27 in rats submitted to resistance exercise (RE). Forty Wistar rats were distributed into 5 groups: sedentary; trained (CTRL); and trained supplemented with l-alanyl-l-glutamine, l-glutamine and l-alanine in their free form (GLN+ALA), or free l-alanine (ALA). All trained animals were submitted to a 6-week ladder-climbing protocol. Supplementations were offered in a 4% drinking water solution for 21 days prior to euthanasia. Plasma glutamine, creatine kinase (CK), myoglobin (MYO), and erythrocyte concentration of reduced GSH and glutathione disulfide (GSSG) were measured. In tibialis anterior skeletal muscle, GLN-GSH axis, thiobarbituric acid reactive substances (TBARS), and the expression of heat shock factor 1 (HSF-1), 27-kDa heat shock protein (HSP-27), and glutamine synthetase were determined. In CRTL animals, high-intensity RE reduced muscle glutamine levels and increased GSSG/GSH rate and TBARS, as well as augmented plasma CK and MYO levels. Conversely, l-glutamine-supplemented animals showed an increase in plasma and muscle levels of glutamine, with a reduction in GSSG/GSH rate, TBARS, and CK. Free l-alanine administration increased plasma glutamine concentration and lowered muscle TBARS. HSF-1 and HSP-27 were high in all supplemented groups when compared with CTRL (p < 0.05). The results presented herein demonstrate that l-glutamine supplemented with l-alanine, in both a free or dipeptide form, improve the GLN-GSH axis and promote cytoprotective effects in rats submitted to high-intensity RE training.

Effects of supplementation with L-glutamine and L-alanine in the body composition of rats submitted to resistance exercise / Efeitos da suplementação com L-glutamina e L-alanina na composição corporal de ratos submetidos ao exercício resistido / Efectos de la suplementación con L-glutamina y L-alanina en la composición corporal de ratones sometidos a ejercicio de resistencia

Abstract We investigated the effects of glutamine and alanine supplementation on body composition of rats submitted to resistance exercise. Wistar rats were submitted to eight-week of resistance exercise, which consisted of climbing a ladder with progressive loads (25-100% of body weight). In the last 21 days of training, animals were supplemented with L-glutamine and L-alanine, as a dipeptide or in their free form (DIP, GLN + ALA and ALA groups), or water (SED and CTRL groups). RE attenuated body weight gain and lipid contents of CTRL group (p < 0.05 vs. SED) and DIP supplementation promoted an increase in tibialis muscle weight, as well as in protein content (p < 0.05 vs. CTRL). Taken together, our data indicated that resistance exercise improves body composition and dipeptide potentiated the muscle hypertrophic effect.

Resumo Foram investigados os efeitos da suplementação com glutamina e alanina na composição corporal de ratos submetidos a exercício resistido. Ratos Wistar foram submetidos, durante oito semanas, ao exercício resistido, que consistia em subir uma escada com cargas progressivas (25 a 100% do peso corporal). Nos últimos 21 dias de treinamento, os animais foram suplementados com L-glutamina e L-alanina, como dipeptídeo ou em sua forma livre (DIP, GLN + ALA ALA e grupos) ou água (grupos SED e CTRL). Exercício resistido atenuou o ganho de peso corporal e conteúdo lipídico do CTRL (p < 0,05 vs. SED) e o DIP promoveu aumento no peso do músculo tibial, bem como no teor de proteína (p < 0,05 vs. CTRL). Os nossos dados indicam que o exercício resistido, melhora a composição corporal e dipeptídeo potencializa o efeito hipertrófico muscular.

Resumen Se investigaron los efectos de la glutamina y la alanina en la composición corporal de ratones sometidos a ejercicio de resistencia. Algunos ratones Wistar fueron sometidos a 8 semanas de ejercicio de resistencia, que consistía en subir una escalera con cargas progresivas (del 25 al 100% de la masa corporal). En los últimos 21 días, los animales recibieron un suplemento de L-glutamina y L-alanina, en forma de dipéptido o en su forma libre (grupos DIP, GLN + ALA y ALA) o agua (grupos SED y CTRL). El ejercicio de resistencia redujo el aumento de masa corporal y la concentración de lípidos del CTRL (p <0,05 vs. SED). La suplementación con DIP promovió un aumento de peso del músculo tibial, así como en el contenido de proteína (p < 0,05 frente a CTRL). Nuestros resultados indican que el ejercicio de resistencia mejora la composición corporal y el DIP potencia el efecto hipertrófico.

Associação entre alimentação, ansiedade, depressão e estado nutricional: efeitos sobre absenteísmo e despesas em saúde entre indivíduos adultos residentes no município de São Paulo (SP) / Association between diet, anxiety, depression, and nutritional status: effects on absenteeism and health expenses among adult individuals living in the city of São Paulo

INTRODUÇÃO: O sobrepeso e a obesidade são situações marcadas pelo acúmulo excessivo de gordura corporal, sendo importante fator de risco para saúde mental dos indivíduos, assim como morbidade e mortalidade por doenças crônicas não-transmissíveis (DCNT). Ansiedade e depressão têm sido condições psicológicas comumente associadas ao sobrepeso e à obesidade. Evidências recentes apontam para efeitos da qualidade da dieta e alguns dos componentes específicos da alimentação sobre sobrepeso, obesidade e saúde mental dos indivíduos. O acúmulo de múltiplas morbidades resulta em agravamento da situação de saúde do indivíduo, gerando ocorrência de diversas comorbidades, perda de qualidade de vida e absenteísmo nas atividades rotineiras, que resultam em elevação dos gastos com saúde que oneram o indivíduo, a sociedade e o sistema de saúde. OBJETIVO: Avaliar associação entre excesso de peso, depressão, ansiedade e dieta e sua relação com absenteísmo e gastos em saúde entre indivíduos adultos residentes no município de São Paulo entre 2003 e 2015. METODOLOGIA: A associação entre excesso de peso, depressão, ansiedade e dieta em relação ao absenteísmo e aos gastos em saúde foi avaliada a partir da análise de dados de 1.976 indivíduos adultos, entrevistados na pesquisa domiciliar Inquérito de Saúde do Município de São Paulo (ISA-Capital), conduzida nos anos de 2003, 2008 e 2015. Sobrepeso e obesidade foram estimados a partir do Índice de Massa Corporal, utilizando-se classificação da Organização Mundial da Saúde. Ansiedade e depressão foram identificadas por meio de questões específicas na seção de doenças autorreferidas pelos indivíduos. Perdas produtivas foram identificadas em termos de absenteísmo em atividades rotineiras por motivos de saúde especificamente vinculados às morbidades em avaliação. A qualidade da dieta foi avaliada por meio de aplicação do Índice de Qualidade da Dieta - Revisado (IQD-R), obtido a partir da análise de dados de consumo alimentar via recordatório 24 horas. Variáveis de controle relativas a demais características pessoais, domiciliares e socioeconômicas foram inseridas na análise, incluindo fatores de risco modificáveis (atividade física, consumo de álcool e tabagismo), deficiências físicas e autoavaliação do estado de saúde. RESULTADOS: A prevalência de depressão aumentou 67,8% no período avaliado e a ocorrência de ansiedade teve elevação de 0,89% em 2003 para 11,11% em 2015. A prevalência de excesso de peso aumentou 51,38%, atingindo 72,89% dos indivíduos no ano de 2015. A prevalência de absenteísmo por motivo de saúde aumentou 77,7% entre 2008 e 2015. A ingestão de vitamina B6 demonstrou associação negativa em relação à depressão, enquanto a obesidade e o alto consumo de gorduras, álcool e açúcar de adição aumentaram quase três e quatro vezes, respectivamente, a chance de depressão. Ocorrência de transtornos psicológicos e presença de ao menos uma doença crônica apresentaram associação positiva com absenteísmo. Maior IQD-R, idade, possuir religião e atingir recomendação de prática de atividade física no lazer foram negativamente associados ao absenteísmo. Excesso de peso, ocorrência de transtornos psicológicos, presença de ao menos uma doença crônica e renda foram fatores positivamente associados aos gastos com saúde. Por outro lado, a cor da pele autorreferida e IQD-R foram fatores associados à redução de gastos em saúde. CONCLUSÃO: Os achados do presente estudo buscaram auxiliar na identificação de fatores de risco e proteção para condição de transtornos psicológicos associados ao sobrepeso e à obesidade, resultando em co-ocorrência de múltiplas morbidades com pior prognóstico ao indivíduo. As evidências contribuem para melhorias na elaboração e implementação de estratégias de políticas públicas para refrear avanços da prevalência de sobrepeso e obesidade, buscando reduzir risco para ocorrência de DCNT na população do município de São Paulo.

INTRODUCTION: Overweight and obesity are situations marked by excessive accumulation of body fat, comprising an important risk factor for the individuals mental health, as well as morbidity and mortality due to chronic non-communicable diseases (CNCD). Anxiety and depression have been the psychological conditions commonly associated with overweight and obesity. Recent evidence points to the effects of diet quality and certain specific components on overweight, obesity, and mental health of individuals. The overlap of multiple morbidities results in worsening of individuals health status, generating the occurrence of diverse comorbidities, loss of the quality of life, and absenteeism in daily activities, which result in increase of health expenditures that burden the individual, the society, and the health system. OBJECTIVE: To analyze the association among overweight, depression, anxiety, and diet in relation with absenteeism and health expenditures among adult individuals living in the municipality of São Paulo between 2003 and 2015. METHODOLOGY: The association among overweight, depression, anxiety, and diet in relation to absenteeism and health expenditures was assessed using data from 1,976 adult individuals interviewed in the Health Survey of Sao Paulo (ISA-Capital), conducted in the years 2003, 2008 and 2015. Overweight and obesity were estimated using the Body Mass Index, using the categorization of the World Health Organization. Anxiety and depression were identified through specific questions in self- reported diseases section of the questionnaire. Productive losses were identified through absenteeism in daily activities due to health problems specifically linked with morbidities under assessment in the study. The quality of the diet was assessed using the Brazilian Healthy Eating Index Revised (BHEI-R), obtained through analysis of food consumption via 24-hour recall. Control variables referring to personal, household, and socioeconomic characteristics were included in the analysis, encompassing modifiable risk factors (physical activity, alcohol consumption, and smoking), physical deficiency, and self-assessment of health status. RESULTS: The prevalence of depression increased 67.8% in the period analyzed, and occurrence of anxiety increased from 0.89% in 2003 to 11.11% in 2015. The prevalence of overweight increased 51.38%, reaching 72.89% of the adult individuals in 2015. The prevalence of absenteeism due to health problems increased 77.7% between 2008 and 2015. The intake of B6 vitamin showed negative association with depression, whilst obesity and high consumption of high consumption of fats, alcohol and added sugar increased approximately three and four times the chance of depression, respectively. Occurrence of psychological problems and declaring at least one chronic disease presented positive association with absenteeism. Higher BHEI-R score, age, having religion, and achieving the recommendation of physical activity during leisure were negatively associated with absenteeism. Overweight, occurrence of psychological problems, declaring at least one chronic disease and income were factors positively associated with health expenditures. On the other hand, self-declared skin color and higher BHEI-R was associated with reduction of health expenditures. CONCLUSION: The findings of the study identified risk and protection factors in relation to psychological problems associated with overweight and obesity, resulting in co-occurrence of multiple morbidities with worst prognosis to individuals. The evidence seeks to contribute for improvements in the design and implementation of strategies in public policies to tackle advances in the prevalence of overweight and obesity by reducing the risk of occurrence of CNCD in the population of Sao Paulo municipality.