Melatonin treatment and its association with pioglitazone improves metabolic response in subcutaneous, periepididymal and retroperitoneal adipose tissue in diabetic rats.

Diabetes mellitus é uma doença resultante da baixa sensibilidade à insulina ou insuficiência da célula beta pancreática ou da associação dos dois fatores. Ratos com diabetes induzida por estreptozotocina durante o período neonatal no quinto dia de idade desenvolvem o quadro diabético clássico de hiperglicemia, hipoinsulinemia, poliúria, polidipsia agravada pela resistência à insulina na vida adulta. Neste estudo, foi investigado se o efeito de longo prazo do tratamento com melatonina e a sua associação com a pioglitazona pode melhorar a resistência à insulina e outras desordens metabólicas nesses animais. Após o desmame, os animais foram divididos nos seguintes grupos: grupo controle (C) - animais saudáveis controle; grupo diabético (D) - animais diabéticos sem tratamento adicional; grupo melatonina (M) - ratos diabéticos tratados com melatonina (1mg/kg); grupo melatonina mais pioglitazona (MP) - ratos diabéticos tratados com melatonina (1mg/kg) e pioglitazona (5mg/kg). Quando adultos (12ª semana de idade) animais foram sacrificados e os tecidos adiposos subcutâneos (SC), epididimal (EP) e retroperitoneal (RP) foram retirados, pesados e processados para isolamento dos adipócitos para avaliar a taxa de captação de glicose, oxidação de glicose e incorporação em lipídios. Amostras de sangue foram coletadas para dosagens bioquímicas. Tratamento com melatonina, associada ou não com pioglitazona, reduziu a hiperglicemia, polidipsia e polifagia, assim como a resistência à insulina, como demonstrado por KITT e HOMA. No entanto, o tratamento com melatonina não conseguiu recuperar a deficiência de peso corporal, da massa de gordura e tamanho dos adipócitos de animais diabéticos. Os níveis de adiponectina e frutosamina foram completamente recuperados pelo tratamento com melatonina, associada ou não com pioglitazona, enquanto nem o nível de insulina plasmática, nem a capacidade de secreção de insulina foram melhorados nos animais diabéticos tratados. Além disso, a melatonina causou um atraso significativo no desenvolvimento sexual deixando as estruturas sexuais menores do que as dos animais diabéticos não tratados. O tratamento com melatonina, associado ou não à pioglitazona, melhorou a responsividade dos adipócitos à insulina dos animais diabéticos, como mostrado no teste de captação de glicose (SC, PE e PR), nos testes de oxidação da glicose e incorporação de glicose em lípidos (PE e RP), um efeito que parece ser parcialmente relacionado com um aumento da expressão de substrato receptor de insulina 1 (IRS1), acetil-coenzima-A carboxilase (ACC) e ácido graxo sintase (FAS). Os animais do grupo D apresentaram menor capacidade basal lipolítica no tecido PE em relação ao grupo C, enquanto o tratamento com melatonina associada à pioglitazona foi capaz de restaurar essa capacidade. Finalmente, os animais tratados com melatonina mostraram expressão gênica aumentada de IR, C/EBPα e FAS, e o grupo MP mostraram expressão gênica aumentada de G6PDH e C/EBPα. Em conclusão, o tratamento com melatonina foi capaz de atenuar as anormalidades metabólicas neste modelo de diabetes, incluindo a resistência à insulina, e promoveu um controle glicêmico a longo prazo.Diabetes mellitus is a disease resulting from low insulin sensibility or pancreatic beta-cell insufficiency or the association of the two factors. Rats with streptozotocin-induced diabetes during the neonatal period by the fifth day of age develop the classic diabetic picture of hyperglycemia, hypoinsulinemia, polyuria, polydipsia aggravated by insulin resistance in adulthood. In this study, we investigated whether the effect of long-term treatment with melatonin and its association with pioglitazone can improve insulin resistance and other metabolic disorders in these animals. After weaning, the animals were divided into the following groups: control group (C) healthy control animals, diabetic group (D) - diabetic animals without additional treatment, melatonin group (M) - diabetic rats treated with melatonin (1mg/kg); melatonin plus pioglitazone group (MP) - diabetic rats treated with melatonin (1mg/kg) and pioglitazone (5mg/kg). When adults (12th week of age) animals were then sacrificed and the subcutaneous (SC), epididymal (EP) and retroperitoneal (RP) fat pads were excised, weighed and processed for adipocyte isolation for assessing glucose uptake, oxidation and incorporation into lipids. Blood samples were collected for biochemical assays. Melatonin treatment, associated or not with pioglitazone, reduced hyperglycemia, polydipsia, and polyphagia as well as improved insulin resistance as demonstrated by KITT and HOMAir. However, melatonin treatment was unable to recover body weight deficiency, fat mass and adipocyte size of diabetic animals. Adiponectin and fructosamine levels were completely recovered by melatonin treatment, associated or not with pioglitazone, while neither plasma insulin level nor insulin secretion capacity were improved in diabetic animals. Furthermore, melatonin caused a marked delay in the sexual development leaving genital structures smaller than those of non-treated diabetic animals. Melatonin treatment, associated or not with pioglitazone, improved the adipocyte responsiveness to insulin in diabetic animals as shown in glucose uptake (SC, EP and RP), glucose oxidation and incorporation of glucose into lipids (EP and RP) tests, an effect that seemed to be partially related to an increased expression of insulin receptor substrate 1 (IRS1), acetyl-coenzyme-A carboxylase (ACC) and fatty acid synthase (FAS). Animals from group D showed a lower basal lipolytic capacity in tissue PE compared to group C, while treatment with melatonin associated with pioglitazone was able to restore this capability. Finally, animals treated with melatonin showed increased gene expression of IR, C/EBPα and FAS, and group MP showed increased gene expression of G6PDH and C/EBPα. In conclusion, melatonin treatment was capable of ameliorating the metabolic abnormalities in this particular diabetes model, including insulin resistance and promoting a better long-term glycemic control

Are sleep time and quality associated with inflammation in children and adolescents? A systematic review

Sleep restriction in children can trigger the development of problems such as impaired cognition, behavioral problems, cardiovascular problems, and obesity. In addition, the inflammatory profile of children can also be influenced by sleep restriction. The aimed to review and analyze the association between time and sleep quality with inflammatory biomarkers in children and adolescents. Three electronic databases (MEDLINE, Web of Science and Scopus) were searched from August 30, 2022. The search strategy used the following descriptors: children and adolescents; sleep, and inflammatory profile. This review protocol is registered in the PROSPERO database (CRD42020188969). We obtained 2.724 results of articles with potentially relevant titles. Sixteen percent of the articles were excluded because they were duplicates, 84.3% were excluded after reading the title, and 0.9% were studied from systematic reviews or textbooks (0.9%). Accelerometers are the most commonly used method for the objective measurement of sleep time, while the PSQI questionnaire is the most commonly used subjective method to measure sleep quality. The results indicated an inconsistent association between sleep time and CRP in the literature. Sixty percent of studies used the Pittsburgh Sleep Quality Index (PSQI) for subjective assessment of sleep quality and possible sleep disorders. However, only one retrieved study showed significant association between sleep quality and CRP. Thus, sleep time does not present significant association with inflammatory biomarkers; whereas, poor sleep quality shows positive association with CRP with a lower magnitude

Alimentação pré-exercício e sintomas de desconforto gastrointestinais durante treinamento de natação

Food intake before physical activity can cause various gastrointestinal symptoms during sports practice and negatively influence the athlete's health and performance. This study aimed to investigate the relationship between pre-exercise eating and gastrointestinal / physical discomfort symptoms of 29 master swimming athletes. The 24-hour food recall was used. Record of gastrointestinal / physical symptoms during training was obtained by questionnaire after an exercise session. Questionnaires were checked if athletes reported symptoms during training, such as fainting, dizziness, nausea, vomiting, diarrhea, distended abdomen / bloating, belching and / or intestinal gas, heartburn, stomach / intestinal pain, feeling weak or tired, feeling hungry. Most athletes had some symptoms of gastrointestinal / physical discomfort during exercise. A positive relationship was observed between higher protein intake and the presence of a higher number of gastrointestinal / physical symptoms. The most prevalent symptom was the feeling of weakness / physical tiredness. It was concluded that as a result of pre-exercise diet there was inadequate carbohydrate intake, and a relationship between increased protein intake and the appearance of symptoms of gastrointestinal / physical discomfort during swimming training.O consumo alimentar antes da atividade física pode provocar diversos sintomas gastrointestinais durante a prática da atividade esportiva e influenciar negativamente na saúde e no desempenho do atleta. Este estudo objetivou investigar a relação entre a alimentação pré-exercício e os sintomas de desconforto gastrointestinais/físicos de 29 atletas de natação máster. Foi utilizado o recordatório alimentar de 24 horas. O registro de sintomas gastrointestinais/físicos durante o treinamento foi obtido por questionário após uma sessão de exercício. Foi verificado, por meio de questionário, se os atletas relatavam sintomas durante o treinamento, como: sensação de desmaio, tontura, náuseas, vômito, diarreia, abdômen distendido/inchaço, arrotos e/ou gases intestinais, azia, dor estomacal/intestinal, sensação de fraqueza ou cansaço, sensação de fome. A maioria dos atletas apresentou algum sintoma de desconforto gastrointestinal/físico durante o exercício. Foi observada relação positiva entre o maior consumo de proteínas e a presença de um maior número de sintomas gastrointestinais/físicos. O sintoma mais prevalente foi a sensação de fraqueza/cansaço físico. Conclui-se que em decorrência da alimentação pré-exercício houve a inadequação do consumo de carboidratos, e relação entre o consumo aumentado de proteína com o aparecimento de sintomas de desconforto gastrointestinais/físicos durante o treinamento de natação

Identification of intracellular peptides in rat adipose tissue: Insights into insulin resistance

Intracellular peptides generated by the proteasome and oligopeptidases have been suggested to function in signal transduction and to improve insulin resistance in mice fed a high-caloric diet. The aim of this study was to identify specific intracellular peptides in the adipose tissue of Wistar rats that could be associated with the physiological and therapeutic control of glucose uptake. Using semiquantitative mass spectrometry and LC/MS/MS analyses, we identified ten peptides in the epididymal adipose tissue of the Wistar rats; three of these peptides were present at increased levels in rats that were fed a high-caloric Western diet (WD) compared with rats fed a control diet (CD). The results of affinity chromatography suggested that in the cytoplasm of epididymal adipose tissue from either WD or CD rats, distinctive proteins bind to these peptides. However, despite the observed increase in the WD animals, the evaluated peptides increased insulin-stimulated glucose uptake in 3T3-L1 adipocytes treated with palmitate. Thus, intracellular peptides from the adipose tissue of Wistar rats can bind to specific proteins and facilitate insulin-induced glucose uptake in 3T3-L1 adipocytes.Brazilian National Research Council (CNPq) [559698/2009-7-Rede GENO-PROT]Brazilian National Research Council (CNPq)University of Sao Paulo (NAPNAUSP)University of Sao Paulo (NAPNA-USP) [2011.1.9333.1.3]CNPqCNPqSao Paulo State Research Foundation (FAPESP)Sao Paulo State Research Foundation (FAPESP

Pinealectomy interferes with the circadian clock genes expression in white adipose tissue

Melatonin, the main hormone produced by the pineal gland, is secreted in a circadian manner (24-hr period), and its oscillation influences several circadian biological rhythms, such as the regulation of clock genes expression (chronobiotic effect) and the modulation of several endocrine functions in peripheral tissues. Assuming that the circadian synchronization of clock genes can play a role in the regulation of energy metabolism and it is influenced by melatonin, our study was designed to assess possible alterations as a consequence of melatonin absence on the circadian expression of clock genes in the epididymal adipose tissue of male Wistar rats and the possible metabolic repercussions to this tissue. Our data show that pinealectomy indeed has impacts on molecular events: it abolishes the daily pattern of the expression of Clock, Per2, and Cry1 clock genes and Ppar expression, significantly increases the amplitude of daily expression of Rev-erb, and affects the pattern of and impairs adipokine production, leading to a decrease in leptin levels. However, regarding some metabolic aspects of adipocyte functions, such as its ability to synthesize triacylglycerols from glucose along 24hr, was not compromised by pinealectomy, although the daily profile of the lipogenic enzymes expression (ATP-citrate lyase, malic enzyme, fatty acid synthase, and glucose-6-phosphate dehydrogenase) was abolished in pinealectomized animals.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ São Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508000 São Paulo, SP, BrazilUniversidade Federal de São Paulo, Dept Physiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol, São Paulo, BrazilFAPESP: 2010/20719-1Web of Scienc