Dose- and time-dependent alterations in lipid metabolism after pharmacological PGC-1α activation in L6 myotubes

J Cell Physiol. 2019 Jul;234(7):11923-11941. doi: 10.1002/jcp.27872. Epub 2018 Dec 6.

Abstract

Pyrroloquinoline quinone (PQQ) acts as a powerful modulator of PGC-1α activation and therefore regulates multiple pathways involved in cellular energy homeostasis. In the present study, we assessed the effects of L6 myotubes incubation with 0.5, 1, and 3 μM PQQ solution for 2 and 24 hr with respect to the cells' lipid metabolism. We demonstrated that PQQ significantly elevates PGC-1α content in a dose- and time-dependent manner with the highest efficiency for 0.5 and 1 µM. The level of free fatty acids was diminished (24 hr: -66%), while an increase in triacylglycerol (TAG) amount was most pronounced after 0.5 μM (2 hr: +93%, 24 hr: +139%) treatment. Ceramide (CER) content was elevated after 2 hr incubation with 0.5 µM and after prolonged exposure to all PQQ concentrations. The cells treated with PQQ for 2 hr exhibited decreased sphinganine (SFA) and sphinganine-1-phosphate (SFA1P) level, while 24 hr incubation resulted in an elevated sphingosine (SFO) amount. In summary, PGC-1α activation promotes TAG and CER synthesis.

Keywords: DAG; FFA; L6 myotubes; PGC-1α; TAG; pyrroloquinoline quinone; sphingolipids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ceramides / metabolism
  • Lipid Metabolism / drug effects
  • Lipid Metabolism / physiology*
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / metabolism*
  • PQQ Cofactor / pharmacology*
  • Trans-Activators / drug effects
  • Trans-Activators / metabolism
  • Transcription Factors / drug effects
  • Transcription Factors / metabolism
  • Triglycerides / metabolism

Substances

  • Ceramides
  • Trans-Activators
  • Transcription Factors
  • Triglycerides
  • PQQ Cofactor