title: Caloric restriction-mediated induction of lipid metabolism gene expression in liver is enhanced by Keap1-knockdown.
abstract: OBJECTIVE
  CR increases fatty acid oxidation to decrease tissue lipid content. The Nuclear factor E2-related factor 2 (Nrf2)-Kelch like ECH associated Protein 1 (Keap1) pathway is an antioxidant gene regulatory pathway that has been previously investigated in weight gain. However, limited interaction of Nrf2/Keap1 and CR exists. The purpose of this study was to determine how Keap1 knockdown (Keap1-KD), which is known to increase Nrf2 activity, affects the CR response, such as weight loss, hepatic lipid decrease, and induction of fatty acid oxidation gene expression.
  
  
  METHODS
  C57BL/6 and Keap1-KD mice were maintained on 40% CR or fed ad libitum for 6 weeks. Hepatic lipid content, lipid metabolic gene, and miRNA expression was quantified.
  
  
  RESULTS
  CR lowered hepatic lipid content, and induced fatty acid oxidation gene expression to a greater degree in Keap1-KD compared to C57BL/6 mice. CR differentially altered miRNA 34a, 370, let-7b* in livers of Keap1-KD compared to C57BL/6 mice.
  
  
  CONCLUSIONS
  CR induced induction of fatty acid oxidation gene expression was augmented with Keap1 knockdown, which was associated with differential expression of several miRNAs implicated in fatty acid oxidation and lipid accumulation.
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, 7 Greenhouse Road, Kingston, Rhode Island 02881, USA.
authors.forename: Supriya R
authors.initials: SR
authors.lastname: Kulkarni
authors.forename: Laura E
authors.initials: LE
authors.lastname: Armstrong
authors.forename: Angela L
authors.initials: AL
authors.lastname: Slitt
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000818:Animals; D031204:Caloric Restriction; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005227:Fatty Acids / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D000072019:Kelch-Like ECH-Associated Protein 1; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics; D010084:Oxidation-Reduction; D015431:Weight Loss
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D005227:Fatty Acids; C117301:Keap1 protein, mouse; D000072019:Kelch-Like ECH-Associated Protein 1; D008055:Lipids; D035683:MicroRNAs