Metabolic profile assessment in subjects with overweight and obesity in glutamine oral supplementation

Orientador: Patrícia de Oliveira PradaDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências AplicadasResumo: A obesidade é uma doença metabólica crônica caracterizada pelo excesso de gordura corporal e é considerada como um grande fator de risco para o desenvolvimento de diabetes mellitus tipo 2 (DM2). A International Diabetes Federation (IDF) estima que o Brasil tenha 13,4 milhões de pessoas (8,7% da população) com diabetes. Um aspecto fundamental na etiologia do DM2 é a resistência à insulina que possui uma grande relação com obesidade e sedentarismo. Recentes descobertas têm demonstrado que alterações nas concentrações de metabólitos sanguíneos podem predizer o risco de desenvolvimento do DM2. Estudos apontam uma forte associação entre os níveis séricos de aminoácidos de cadeia ramificada (AACR) e o desenvolvimento de resistência à insulina associada à obesidade. Os AACR compreendem três aminoácidos essenciais: leucina, isoleucina e valina. Estes aminoácidos têm sido reconhecidos como um dos principais moduladores da ação da insulina, pois atua no complexo da proteína mammalian target of rapamycin (mTOR). Frente a este panorama, alguns estudos vêm buscando alternativas nutricionais não farmacológicas que melhorem a resistência à insulina e que auxiliem na prevenção do DM2. Recentemente tem-se pesquisado o papel adicional da glutamina no organismo humano neste contexto. Sendo assim, o objetivo do estudo é investigar se a suplementação oral de glutamina altera o perfil de AACR, tirosina e fenilalanina e se este fenômeno está associado a uma melhor do perfil metabólico de indivíduos com sobrepeso e obesidade. A pesquisa foi desenvolvida no Hospital Estadual Sumaré com a participação de 35 voluntários. Os voluntários foram divididos em dois grupos. O grupo experimental recebeu suplementação de 30 gramas de L-glutamina por via oral durante 14 dias e o grupo controle recebeu alanina na mesma proporção e mesmo período. Foram avaliados os seguintes parâmetros: peso, estatura, circunferência de cintura, consumo alimentar, glicose e insulina séricas, determinação da resistência à insulina e determinação de níveis séricos de aminoácidos. Os níveis de aminoácidos foram determinados pelo método de cromatografia líquida de alta-eficiência com detecção por ultra-violeta (CLAE-UV). Observamos uma redução significativa da medida de circunferência de cintura após o período de suplementação, independentemente do tipo de suplemento. Apenas o aminoácido isoleucina se mostrou significativamente maior após a suplementação com glutamina. Não observamos alterações de outros parâmetros avaliadosAbstract: Obesity is a chronic metabolic disease characterized by excess body fat and is considered a major risk factor for developing type 2 diabetes mellitus (DM2). The International Diabetes Federation (IDF) estimates that Brazil has 13.4 million people (8.7% of the population) with diabetes. A key aspect in the etiology of type 2 diabetes is insulin resistance which has a great relationship with obesity and physical inactivity. Recent findings have shown that changes in blood metabolite concentrations can predict the risk of developing T2DM. Studies suggest a strong association between serum levels of branched chain amino acids (BCAA) and the development of insulin resistance associated with obesity. The BCAA comprise three essential amino acids: leucine, isoleucine and valine. These amino acids have been recognized as a major modulator of insulin action because it acts on the protein complex mammalian target of rapamycin (mTOR). Faced with this panorama, some studies have sought nonpharmacological nutritional alternatives that improve insulin resistance and to assist in the prevention of T2DM. Recently it has been researched additional role of glutamine in the human body in this context. Thus, the objective of the study is to investigate whether oral glutamine supplementation alters the BCAA profile, tyrosine and phenylalanine and this phenomenon is associated with a better metabolic profile of overweight and obesity. The research was conducted at the State Hospital Sumaré attended by 35 volunteers. The volunteers were divided into two groups. The experimental group received a supplement of 30 grams of L-glutamine orally for 14 days and the control group received the same proportion and alanine same period. The following parameters were evaluated: weight, height, waist circumference, food consumption, serum glucose and insulin determination of insulin resistance and determination of serum amino acids. The amino acid levels were determined by liquid chromatography method of high-efficiency ultraviolet detection (HPLC-UV). We observed a significant reduction in the measure of waist circumference after the supplementation period, regardless of the type of supplement. Only the amino acid isoleucine was significantly greater after supplementation with glutamine. We did not observe changes in other parameters evaluatedMestradoMetabolismo e Biologia MolecularMestra em Ciências da Nutrição e do Esporte e Metabolism

Oral Glutamine Supplementation Reduces Obesity, Pro-Inflammatory Markers, and Improves Insulin Sensitivity in DIO Wistar Rats and Reduces Waist Circumference in Overweight and Obese Humans

In the present study, we aimed to investigate whether chronic oral glutamine (Gln) supplementation may alter metabolic parameters and the inflammatory profile in overweight and obese humans as well as whether Gln may modulate molecular pathways in key tissues linked to the insulin action in rats. Thirty-nine overweight/obese volunteers received 30 g of Gln or alanine (Ala-control) for 14 days. Body weight (BW), waist circumference (WC), hormones, and pro-inflammatory markers were evaluated. To investigate molecular mechanisms, Gln or Ala was given to Wistar rats on a high-fat diet (HFD), and metabolic parameters, euglycemic hyperinsulinemic clamp with tracers, and Western blot were done. Gln reduced WC and serum lipopolysaccharide (LPS) in overweight volunteers. In the obese group, Gln diminished WC and serum insulin. There was a positive correlation between the reduction on WC and LPS. In rats on HFD, Gln reduced adiposity, improved insulin action and signaling, and reversed both defects in glucose metabolism in the liver and muscle. Gln supplementation increased muscle glucose uptake and reversed the increased hepatic glucose production, in parallel with a reduced glucose uptake in adipose tissue. This insulin resistance in AT was accompanied by enhanced IRS1 O-linked-glycosamine association in this tissue, but not in the liver and muscle. These data suggest that Gln supplementation leads to insulin resistance specifically in adipose tissue via the hexosamine pathway and reduces adipose mass, which is associated with improvement in the systemic insulin action. Thus, further investigation with Gln supplementation should be performed for longer periods in humans before prescribing as a beneficial therapeutic approach for individuals who are overweight and obese