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Mimetics of caloric restriction include agonists of lipid-activated nuclear receptors.

Publication ,  Journal Article
Corton, JC; Apte, U; Anderson, SP; Limaye, P; Yoon, L; Latendresse, J; Dunn, C; Everitt, JI; Voss, KA; Swanson, C; Kimbrough, C; Wong, JS ...
Published in: J Biol Chem
October 29, 2004

The obesity epidemic in industrialized countries is associated with increases in cardiovascular disease (CVD) and certain types of cancer. In animal models, caloric restriction (CR) suppresses these diseases as well as chemical-induced tissue damage. These beneficial effects of CR overlap with those altered by agonists of nuclear receptors (NR) under control of the fasting-responsive transcriptional co-activator, peroxisome proliferator-activated co-activator 1alpha (PGC-1alpha). In a screen for compounds that mimic CR effects in the liver, we found statistically significant overlaps between the CR transcript profile in wild-type mice and the profiles altered by agonists of lipid-activated NR, including peroxisome proliferator-activated receptor alpha (PPARalpha), liver X receptor, and their obligate heterodimer partner, retinoid X receptor. The overlapping genes included those involved in CVD (lipid metabolism and inflammation) and cancer (cell fate). Based on this overlap, we hypothesized that some effects of CR are mediated by PPARalpha. As determined by transcript profiling, 19% of all gene expression changes in wild-type mice were dependent on PPARalpha, including Cyp4a10 and Cyp4a14, involved in fatty acid omega-oxidation, acute phase response genes, and epidermal growth factor receptor but not increases in PGC-1alpha. CR protected the livers of wild-type mice from damage induced by thioacetamide, a liver toxicant and hepatocarcinogen. CR protection was lost in PPARalpha-null mice due to inadequate tissue repair. These results demonstrate that PPARalpha mediates some of the effects of CR and indicate that a pharmacological approach to mimicking many of the beneficial effects of CR may be possible.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

October 29, 2004

Volume

279

Issue

44

Start / End Page

46204 / 46212

Location

United States

Related Subject Headings

  • Transcription Factors
  • Trans-Activators
  • Risk Factors
  • Receptors, Cytoplasmic and Nuclear
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • PPAR alpha
  • Orphan Nuclear Receptors
  • Mice, Inbred C57BL
  • Mice
  • Male
 

Citation

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Corton, J. C., Apte, U., Anderson, S. P., Limaye, P., Yoon, L., Latendresse, J., … Mehendale, H. M. (2004). Mimetics of caloric restriction include agonists of lipid-activated nuclear receptors. J Biol Chem, 279(44), 46204–46212. https://doi.org/10.1074/jbc.M406739200
Corton, J Christopher, Udayan Apte, Steven P. Anderson, Pallavi Limaye, Lawrence Yoon, John Latendresse, Corrie Dunn, et al. “Mimetics of caloric restriction include agonists of lipid-activated nuclear receptors.J Biol Chem 279, no. 44 (October 29, 2004): 46204–12. https://doi.org/10.1074/jbc.M406739200.
Corton JC, Apte U, Anderson SP, Limaye P, Yoon L, Latendresse J, et al. Mimetics of caloric restriction include agonists of lipid-activated nuclear receptors. J Biol Chem. 2004 Oct 29;279(44):46204–12.
Corton, J. Christopher, et al. “Mimetics of caloric restriction include agonists of lipid-activated nuclear receptors.J Biol Chem, vol. 279, no. 44, Oct. 2004, pp. 46204–12. Pubmed, doi:10.1074/jbc.M406739200.
Corton JC, Apte U, Anderson SP, Limaye P, Yoon L, Latendresse J, Dunn C, Everitt JI, Voss KA, Swanson C, Kimbrough C, Wong JS, Gill SS, Chandraratna RAS, Kwak M-K, Kensler TW, Stulnig TM, Steffensen KR, Gustafsson J-A, Mehendale HM. Mimetics of caloric restriction include agonists of lipid-activated nuclear receptors. J Biol Chem. 2004 Oct 29;279(44):46204–46212.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

October 29, 2004

Volume

279

Issue

44

Start / End Page

46204 / 46212

Location

United States

Related Subject Headings

  • Transcription Factors
  • Trans-Activators
  • Risk Factors
  • Receptors, Cytoplasmic and Nuclear
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • PPAR alpha
  • Orphan Nuclear Receptors
  • Mice, Inbred C57BL
  • Mice
  • Male