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Activation of AMP-kinase by Policosanol Requires Peroxisomal Metabolism

  • Original Article
  • Published:
Lipids

Abstract

Policosanol, a well-defined mixture of very long chain primary alcohols that is available as a nutraceutical product, has been reported to lower blood cholesterol levels. The present studies demonstrate that policosanol promotes the phosphorylation of AMP-kinase and HMG-CoA reductase in hepatoma cells and in mouse liver after intragastric administration, providing a possible means by which policosanol might lower blood cholesterol levels. Treatment of hepatoma cells with policosanol produced a 2.5-fold or greater increase in the phosphorylation of AMP-kinase and HMG-CoA reductase, and increased the phosphorylation of Ca++/calmodulin-dependent kinase kinase (CaMKK), an upstream AMP-kinase kinase. Intragastric administration of policosanol to mice similarly increased the phosphorylation of hepatic HMG-CoA reductase and AMP-kinase by greater than 2-fold. siRNA-mediated suppression of fatty aldehyde dehydrogenase, fatty acyl-CoA synthetase 4, and acyl-CoA acetyltransferase expression in hepatoma cells prevented the phosphorylation of AMP-kinase and HMG-CoA reductase by policosanol, indicating that metabolism of these very long chain alcohols to activated fatty acids is necessary for the suppression of cholesterol synthesis, presumably by increasing cellular AMP levels. Subsequent peroxisomal β-oxidation probably augments this effect.

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Abbreviations

CaMKK:

Calcium-calmodulin-dependent kinase kinase

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Acknowledgments

We thank Dr. Geza Bruckner for helpful insight and advice, and numerous anonymous reviewers for their comments and suggestions. This work was supported by the National Institutes of Health National Center for Complementary and Alternative Medicine [Grant AT003488].

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Authors and Affiliations

  1. Graduate Center for Toxicology, University of Kentucky, Lexington, KY, 40536-0305, USA

    Subhashis Banerjee & Todd D. Porter

  2. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, 40536-0596, USA

    Sarbani Ghoshal & Todd D. Porter

Authors
  1. Subhashis Banerjee
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  2. Sarbani Ghoshal
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  3. Todd D. Porter
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Correspondence to Todd D. Porter.

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Banerjee, S., Ghoshal, S. & Porter, T.D. Activation of AMP-kinase by Policosanol Requires Peroxisomal Metabolism. Lipids 46, 311–321 (2011). https://doi.org/10.1007/s11745-011-3540-6

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  • DOI: https://doi.org/10.1007/s11745-011-3540-6

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