title: Short-term inhibition of SREBP-1c expression reverses diet-induced non-alcoholic fatty liver disease in mice.
abstract: OBJECTIVE
  The present study investigates the level of Sterol-regulatory element-binding proteins (SREBP-1c) and related proteins in obese mice (DIO) treated with SREBP-1c antisense oligonucleotide (ASO) to observe a reversal of steatosis.
  
  
  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. After a period of 24 h following the last injection mice were killed and plasma and hepatic tissue were obtained to evaluate plasma triglycerides and total liver fat. Western blot was performed to evaluate SREBP-1c, FAS, SCD-1, PPARγ and CPT1 expression and AMPK[Thr172] and ACC[Ser79] phosphorylation. Livers were stained using the hematoxylin and eosin method for histological analysis.
  
  
  RESULTS
  Body weight, epididymal fat and glucose levels were not affected by one daily dose of ASO. 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 and SCD-1. Moreover, mice treated with ASO presented a significant reduction in macroscopic and microscopic features of hepatic steatosis.
  
  
  CONCLUSIONS
  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 in mice.
authors.affiliation: Laboratory of Exercise Biochemistry and Physiology, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.
authors.forename: Marisa Js
authors.initials: MJ
authors.lastname: Frederico
authors.forename: Marcelo F
authors.initials: MF
authors.lastname: Vitto
authors.forename: Patrícia A
authors.initials: PA
authors.lastname: Cesconetto
authors.forename: Julia
authors.initials: J
authors.lastname: Engelmann
authors.forename: Daniela R
authors.initials: DR
authors.lastname: De Souza
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Luz
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Pinho
authors.forename: Eduardo R
authors.initials: ER
authors.lastname: Ropelle
authors.forename: Dennys E
authors.initials: DE
authors.lastname: Cintra
authors.forename: Cláudio T
authors.initials: CT
authors.lastname: De Souza
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000737:chemistry; D000103:Acetyl-CoA Carboxylase / Q000737:chemistry; D050154:Adiposity; D000818:Animals; D064429:Fatty Acid Synthases / Q000378:metabolism; D005234:Fatty Liver / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008820:Mice, Obese; D065626:Non-alcoholic Fatty Liver Disease; D016376:Oligonucleotides, Antisense / Q000494:pharmacology* / Q000627:therapeutic use; D047495:PPAR gamma / Q000378:metabolism; D010766:Phosphorylation; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood
chemical_list: D016376:Oligonucleotides, Antisense; D047495:PPAR gamma; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase; D064429:Fatty Acid Synthases; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase