Efeito da inibição da expressão da srebp-1c na reversão da doença do fígado gorduroso induzido por dieta hiperlipídica

Abstract

Objective. The present study investigated the level of Sterol regulatory element binding proteins (SREBP-1c) and related proteins in obese mice treated with SREBP-1c oligonucleotide to observe a reversal of steatosis. Materials and methods. Swiss mice were fed on chow containing 61 kJ% saturated fat for 8 weeks to develop obesity. After this period, one group of animals was used to assess the molecular effects of SREBP-1c antisense oligonucleotide treatment by immunoblot analysis in a dose–response curve (0; 1.0; 2.0; 3.0; 4.0 nmol/day). After the dose (3.0 nmol/day) was determined, another group was treated for 14 days. Twenty-four hours after the last injection mice were killed and plasma and hepatic tissue were obtained to evaluate plasma triglycerides and total liver fat. Samples were blotted with anti-SREBP-1c, FAS, SCD-1, PPAR_, ACC[Ser79] phosphorylation, CPT1, and [Thr172]-phosphorylation of AMPK antibodies. Livers were stained using the haematoxylin method for histological analysis. Results. Body weight, epididymal fat and glucose levels were not affected by one daily dose of SREBP-1c/AS. However, total plasma triglycerides and total liver fat were significantly reduced. Also, this treatment inhibited SREBP-1c and reduced protein levels of a series of proteins involved in lipogenesis, including ACC, FAS, SCD-1. Moreover, mice treated with SREBP-1c/AS presented a significant reduction in macroscopic and microscopic features of hepatic steatosis. Conclusion. Our results demonstrate that the inhibition of SREBP-1c decreased the expression of lipogenic enzymes, reducing the accumulation of triglycerides and, finally, reversing hepatic steatosis. Thus, SREBP-1c is an attractive target for pharmacological therapeutics in fatty liver.