Metabolismo da glicose no músculo esquelético e tecido adiposo visceral de animais obesos-induzidos por redução de ninhada submetidos ao exercício crônico precoce de natação

Abstract

Resumo: Lactacao e considerada um periodo critico do desenvolvimento para o organismo sendo uma das janelas de programacao metabolica. Intervencoes hormonais ou nutricionais nesta fase podem pre-dispor o organismo a doencas na idade adulta, em especial a obesidade. Associado a obesidade estao diversas comorbidades, das quais se destacam a resistencia a insulina e alteracoes no metabolismo da glicose. O exercicio fisico atua como fator preventivo e de tratamento, capaz de promover alteracoes teciduais que levam a perda de peso e melhora da responsividade a insulina. O presente trabalho investigou o metabolismo da glicose no tecido muscular esqueletico (ME) e adiposo visceral em ratos obesos-induzidos por reducao de ninhada e os efeitos do exercicio fisico cronico precoce nestes animais. Ninhadas de ratos Wistar foram padronizadas em 10 filhotes por ninhada ate o 3o dia de vida, posteriormente foram reajustadas em Grupo Controle (C), 10 filhotes e Grupo Obeso-induzido (OB), 3 filhotes por ninhada. Aos 21 dias houve o desmame e a subdivisao em 4 grupos: controle sedentario (CS), controle exercitados (CE), obeso-induzido sedentario (OBS) e obeso-induzido exercitado (OBE). O protocolo de exercicio fisico consistiu em natacao 3x/semana/30min. Avaliou-se ganho de massa corporal (lactacao e 22-90 dias) e consumo alimentar (22-90 dias). Aos 85 dias foi realizado teste de tolerancia a insulina (ITT). Apos ortotanasia, 90 dias, amostras de tecido foram dissecadas, pesadas e armazenadas. Parametros plasmaticos de glicemia, colesterolemia e triacilglicerolemia foram mensurados. Musculo soleo e tecido adiposo perigonadal foram submetidos a incubacao na presenca ou ausencia de insulina (10mU/ml) com adicao de glicose (5,6 mM), 0,1 uCi / ml de D-[U-14C] glicose e 0,1 uCi / ml de 2-desoxi-D-[3H] glicose, para avaliacao da producao de lactato total e radiomarcado. A expressao proteica do GLUT4(soleo e tecido adiposo) e do PPAR?(depositos viscerais de gordura) foram determinados. O % de acido graxo (AG) do plasma, figado e gorduras perigonadal, retroperitoneal e mesenterica foi identificado e quantificado por HPLC. O conteudo de glicogenio muscular e dos depositos de gordura foi mensurado. Os dados foram expressos como media } SEM, submetidos a analise de variancia ANOVA de duas vias, tendo como fatores a obesidade e exercicio, (pos teste Bonferroni entre pares selecionados) e Teste t de Student's (p<0,05). Houve aumento da massa corporal na lactacao e na vida adulta, acompanhado do aumento dos depositos viscerais e resistencia a insulina nos obesos-induzidos. Nao houve alteracao nos padroes bioquimicos plasmaticos.O musculo soleo apresentou-se responsivo ao estimulo insulinico, comparada a menor responsividade da gordura visceral aos 90 dias.A natacao conteve o aumento dos depositos viscerais, promoveu aumento da gordura marrom e maior sensibilidade a insulina em ambos os grupos exercitados. Houve aumento na expressao do GLUT4 no ME nos animais CE e na gordura visceral de ambos os grupos exercitados. Houve alteracao no % de AG tecidual em funcao da obesidade e do exercicio. Desta forma, o maior aporte calorico promovido pela reducao de ninhada no periodo lactacional favoreceu a instalacao da obesidade, induziu resistencia a insulina e alteracoes no % AG, estando a musculatura ainda responsiva a insulina aos 90dias apresentando alteracoes metabolicas no TA visceral. O exercicio fisico cronico precoce conteve a instalacao da obesidade acompanhado da manutencao da responsividade a insulina na ME. Palavras-chave: Obesidade. Programacao metabolica. Musculo. Tecido adiposo. Lipidios.

Abstract: Lactation is considered a critical period of development for the body being one of the windows of metabolic programming. Hormonal or nutritional interventions at this stage may pre-dispose the body to diseases in adulthood, especially obesity. Associated with obesity are several comorbidities, such as insulin resistance and changes in glucose metabolism. Physical exercise acts as a preventive and treatment factor, capable of promoting tissue changes that lead to weight loss and improved insulin responsiveness. The present work investigated the metabolism of glucose in skeletal muscle tissue and visceral adipose in obese rats induced by litter reduction and the effects of early physical exercise in these animals. Wistar rats were standardized on 10 pups per litter until the third day of life, later they were readjusted in Control Group (C), 10 pups and Obese-induced Group (OB), 3 pups per litter. At 21 days, weaning and subdivision were performed in four groups: sedentary control (CS), exercised control (CE), obese-induced sedentary (OBS) and obese-induced exercise (OBE). The physical exercise protocol consisted of swimming 3x/week/30min. Body weight gain (lactation and 22-90 days) and food consumption (22-90 days) were evaluated. At the 85th day, an insulin tolerance test (ITT) was performed. After orthatanasia, 90 days, tissue samples were dissected, weighed and stored. Plasma parameters of glycemia, cholesterolemia and triacylglycerol were measured. The soleus muscle and perigonadal adipose tissue were incubated in the presence or absence of insulin (10mU/ml) with addition of glucose (5.6mM), 0,1 uCi/ml D-[U-14C] glucose and 0,1 uCi/ml of 2-deoxy-D-[3H] glucose, for evaluation of total and radiolabelled lactate production. The protein expression of GLUT4 (sole and adipose tissue) and PPARã (visceral fat deposits) were determined. The percent of fatty acid (AG) in plasma, liver and perigonadal, retroperitoneal and mesenteric fats was identified and quantified by HPLC. The content of muscle glycogen and fat deposits was measured. Data were expressed as mean ± SEM, submitted to analysis of variance of two-way ANOVA, including obesity and exercise (Bonferroni test between selected pairs) and Student's t test (p <0,05). There was an increase in body mass in lactation and in adulthood, accompanied by increased visceral deposits and insulin resistance in obese-induced. There was no change in plasma biochemical patterns. The soleus muscle was responsive to the insulin stimulus, compared to the lower responsiveness of visceral fat at 90 days. Swimming contained an increase in visceral deposits, increased brown fat and increased insulin sensitivity in both groups. There was an increase in the expression of GLUT4 in ME in CE animals and visceral fat in both groups. There was alteration in the percentage of tissue AG as a function of obesity and exercise. Thus, the higher caloric intake promoted by litter reduction in the lactational period favored the establishment of obesity, induced insulin resistance and changes in % AG, and the musculature was still responsive to insulin at 90 days presenting metabolic alterations in visceral TA. The early chronic physical exercise contained the installation of obesity accompanied by the maintenance of insulin responsiveness in ME. Key words: Obesity. Metabolic programming. Muscle. Adipose tissue. Lipids.