Análise morfológica do efeito da terapia de curta duração com IGF-1 sobre a esteatose e fibrose hepática em modelo experimental de obesidade induzida por dieta ocidental

Abstract

Non-Alcoholic Fatty Liver Disease (NAFLD) is currently the main cause of chronic liver disease in the world, being strongly associated with obesity. Liver fat accumulation (steatosis) triggers an inflammatory process generated by lipotoxicity and glycotoxicity, leading to cell damage and hepatocytes death. Thus, the activation of resident liver cells leads to extracellular matrix deposition, mainly collagen, inducing fibrogenesis and, in the long term, liver dysfunction. IGF-1 is a hormone which serum levels are decreased in chronic liver disease. Therefore, the present study aimed to evaluate IGF-1 short-period therapy in NAFLD related to Western diet-induced obesity. For this purpose, 21-day-old male Swiss mice were divided into control group (CG, N=8), fed a standard diet, and obese group (GO, N=16), fed a Western diet, rich in saturated fat and simple carbohydrates, for 12 weeks. In the 11th week, part of the animals in the obese group (N=8) received a daily subcutaneous injection of recombinant human IGF-1 (100µg/kg/day) for seven consecutive days (GO+IGF-1). The other mice received saline solution as a control. Our data demonstrated that treatment as short as one week with IGF-1 was able to improve obesity-related biometric and metabolic parameters. In addition, it promoted the recovery of liver parenchyma, reducing steatosis and fibrosis, thus demonstrating an important hepatoprotective action.