Avaliação metabólica e ecográfica dos efeitos do telmisartan no tratamento da doença gordurosa hepática não alcoólica em camundongos alimentados com dieta normolipídica e hiperlipídica

Abstract

Telmisartan is an antihypertensive widely used in the treatment of mild to moderate hypertension, with an excellent safety profile. In recent years, evidence has shown promising effects of Telmisartan in the treatment of non-alcoholic fatty liver disease (NAFLD), a condition widely diagnosed in humans through non-invasive imaging methods such as ultrasonography (US). The aim of the present study was to investigate the role of Telmisartan in the treatment of NAFLD in mice fed with a high fat diet through metabolic and ultrasound parameters. Male FVB / N mice were divided into four groups and fed for 60 days with a normolipid and hyperlipidic diet, followed by treatment with Telmisartan by gavage for 28 days. During the treatment period, body weight and food consumption were measured. At the end of the treatment, the animals were submitted to glucose tolerance and insulin sensitivity tests and ultrasound examination of the liver and epididymal fat pad, with measurement of liver echogenicity and size (longitudinal axis) and of epididymal fat pad thickness. After sacrifice by decapitation, the organs of interest (liver, epididimal and mesenteric fats) were removed and weighed. Blood samples were used for serum and plasma levels of total cholesterol, HDL cholesterol, triglycerides, alanine transaminase and aspartate aminotransferase. Histological analyzes of the liver were also performed. The results demonstrate that Telmisartan significantly reduced liver weight and histological fat infiltration in hepatocytes of animals fed with a high fat diet, and these findings could be estimated in vivo noninvasively by measuring the size and echogenicity of the liver by US. In addition, the weight and the thickness of epididymal fat pad acessed by US was significantly lower in animals fed with a high fat diet and treated with Telmisartan, showing a beneficial effect of the drug in this parameter. Telmisartan also reduced body weight, mesenteric adipose tissue weight, adiposity, serum alanine aminotransferase levels, and improved glucose tolerance and HDL cholesterol. In conclusion, oral treatment with Telmisartan improved metabolism and hepatic steatosis in mice fed with a high fat diet, and echographic parameters such as liver echogenicity, liver longitudinal axis and epididymal fat pad thickness are effective in estimating liver and epididymal fat weight and the degree of fatty infiltration in the liver. These results reinforce the potential of Telmisartan in the treatment of NAFLD and stimulate the use of US in murine models of hepatic steatosis as a noninvasive tool for diagnosis and longitudinal monitoring of animals rather than more invasive techniques.