Pharmaceutical Research

, Volume 30, Issue 9, pp 2221–2231 | Cite as

Caloric Restriction-Mediated Induction of Lipid Metabolism Gene Expression in Liver is Enhanced by Keap1-Knockdown

  • Supriya R. Kulkarni
  • Laura E. Armstrong
  • Angela L. Slitt
Research Paper



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.


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.


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.


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.


caloric restriction gene expression liver Nfe2l2 nuclear receptor 



Acetyl-CoA carboxylase


Acyl-CoA thioesterase 1


Ad libitum


Carnitine palmitoyltransferase 1A


Caloric Restriction


Fatty acid binding protein 4


Fatty acid synthase


Farnesoid X receptor


Glutamate cysteine ligase catalytic subunit, and


Glutathione S-Transferase


insulin receptor


Kelch like ECH-associated Protein 1


Liver x receptor


Non-alcoholic fatty liver disease


NAD(P) H:quinone oxidoreductase


Nuclear factor E2-Related factor 2


Peroxisome proliferator-activated receptor gamma coactivator 1-alpha


Peroxisome Proliferator activated receptor α


RNA induced silencing complex


Stearoyl-CoA desaturase




Sterol regulatory element binding protein 1c

Supplementary material

11095_2013_1138_MOESM1_ESM.docx (154 kb)
ESM 1 (DOCX 153 kb)


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Supriya R. Kulkarni
    • 1
  • Laura E. Armstrong
    • 1
  • Angela L. Slitt
    • 1
  1. 1.Department of Biomedical and Pharmaceutical SciencesUniversity of Rhode IslandKingstonUSA

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