Avaliação dos Efeitos do Resveratrol sobre a Termogênese Adaptativa, a Ativação da Via da Irisina e o Processo de Browning no Tecido Adiposo de Camundongos e Humanos

Abstract

Resveratrol is a polyphenol that has beneficial effects on diseases associated to the body metabolism and aging/longevity in different animal species. The elucidation of the molecular mechanisms modulated by the resveratrol remains unclear. In this context, the present study aimed to evaluate the effects of the oral treatment with resveratrol on the activation of markers involved in the thermogenesis and browning processes and in the activation of the FNDC5/irisin pathway in the adipose tissue of mice and humans. The mice were divided into four groups and fed for eight weeks with standard and high-fat diet alone or associated with resveratrol. During the treatment, information such as body weight, food intake, oxygen consumption and locomotion level were analyzed. Blood samples were taken for the dosage of glucose, insulin, total cholesterol, HDL, triglycerides, resistin, adiponectin and leptin levels. Analysis of the expression of genes involved in the thermogenesis and browning processes and mitochondrial function were performed by qRT-PCR. Next, samples were taken from the white and brown adipose tissues of twenty obese human patients treated or not with resveratrol for four weeks. Furthermore, adipocytes obtained from human and mice tissue were used for primary culture experiments. The results were grouped in two papers. In the first paper it was shown that the oral treatment with resveratrol in mice fed with standard diet, induced a significant decrease of the body adiposity, accompanied by an improvement of the serum levels of total cholesterol and fasting glucose. Moreover, it was possible to observe an increase in the oxygen consumption in the group treated with resveratrol. The molecular analyzes by qRT-PCR showed an increase in the expression levels of the genes involved in thermogenesis, such as UCP1, SIRT1, PTEN and BMP-7 in the brown adipose tissue. In the second paper, mice were treated with standard and high-fat diet associated with resveratrol. Again, the results showed that the resveratrol induced a significant improvement of the metabolic profile, decreasing the body weight and body adiposity, improving the insulin sensitivity and glucose tolerance and reducing the levels of total cholesterol and triglycerides. These results were accompanied by an increase in the expression levels of the markers associated with thermogenesis and browning processes, such as UCP1, PGC1α and PRDM16 in different types of adipose tissues in humans and mice. Furthermore, it was observed an increment of the FNDC5/irisin expression in the subcutaneous and visceral adipose tissue. The increased expression of these markers seems to be at least partially regulated by the SIRT1 as observed in the primary culture of adipocytes. Therefore, it can be concluded that the resveratrol improves the metabolic function of mice fed with standard and high-fat diets, induces an increase in the expression of markers associated with the thermogenesis and browning processes and besides that, induces the activation of the FNDC5/irisin pathway partially dependent of SIRT1.