Coenzyme Q10 increases the fatty acid oxidation through AMPK-mediated PPARα induction in 3T3-L1 preadipocytes

Cell Signal. 2012 Dec;24(12):2329-36. doi: 10.1016/j.cellsig.2012.07.022. Epub 2012 Aug 3.


Coenzyme Q10(CoQ10) is a known anti-adipogenic factor. However, the mechanism by which CoQ10 acts is unclear. In this study, we found that CoQ10 increased the phosphorylation of AMP-activated protein kinase (AMPK) in 3T3-L1preadipocytes. CoQ10 induced an increase in cytoplasmic calcium concentrations, which is reflected by increased Fluo-3 intensity under confocal microscopy recording. Either inhibition of Ca(2+)/calmodulin-dependent protein kinase kinase (CaMKK) or knock-down CaMKK blocked CoQ10-induced AMPK phosphorylation, suggesting the involvement of calcium in CoQ10-mediated AMPK signaling. CoQ10 also increased the expression of peroxisome proliferator-activated receptor alpha (PPARα) at both the mRNA and protein levels. Knock down of AMPK with siRNA or inhibition of AMPK using an AMPK inhibitor compound C blocked CoQ10-induced expression of PPARα, indicating that AMPK plays a critical role in PPARα induction. In addition, CoQ10 increased fatty acid oxidation in 3T3-L1preadipocytes. The promoter activity of PPARα was increased by CoQ10 in an AMPK-dependent fashion. Moreover, the induction of acyl-CoA oxidase (ACO), a target gene of PPARα, was blocked under the PPARα knock down condition. Furthermore, treatment with CoQ10 blocked differentiation-induced adipogenesis. This blockade was not observed under the PPARα knock-down condition. Collectively, these results demonstrate that CoQ10 induces PPARα expression via the calcium-mediated AMPK signal pathway and suppresses differentiation-induced adipogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • AMP-Activated Protein Kinases / antagonists & inhibitors
  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / metabolism*
  • Acyl-CoA Oxidase / metabolism
  • Adipocytes / cytology
  • Adipocytes / metabolism
  • Adipogenesis / drug effects*
  • Animals
  • Calcium / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Kinase / antagonists & inhibitors
  • Calcium-Calmodulin-Dependent Protein Kinase Kinase / genetics
  • Calcium-Calmodulin-Dependent Protein Kinase Kinase / metabolism
  • Fatty Acids / metabolism*
  • Mice
  • Oxidation-Reduction
  • PPAR alpha / genetics
  • PPAR alpha / metabolism*
  • Phosphorylation / drug effects
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Transcription, Genetic
  • Ubiquinone / analogs & derivatives*
  • Ubiquinone / pharmacology


  • Fatty Acids
  • PPAR alpha
  • RNA, Small Interfering
  • Ubiquinone
  • Acyl-CoA Oxidase
  • Calcium-Calmodulin-Dependent Protein Kinase Kinase
  • AMP-Activated Protein Kinases
  • coenzyme Q10
  • Calcium