Effect of metformin and lipid emulsion on the circadian gene expression in muscle cells

Maayan Barnea, Tamar Cohen-Yogev, Nava Chapnik, Zecharia Madar, Oren Froy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


The circadian clock influences nearly all aspects of metabolism. However, little is known regarding the effect of the energy status on circadian rhythms. Our aim was to test the effect of two opposing energy situations, metformin and lipid emulsion (LE), on clock and metabolic circadian expression in differentiated C2C12 myotubes. Metformin treatment led to depleted ATP levels accompanied by elevated NADH levels, whereas LE treatment led to increased ATP and NAD+ levels. Nevertheless, both LE and metformin treatments activated the AMP-activated protein kinase (AMPK) pathway. In contrast, the effect on circadian rhythms was completely different. LE led to disrupted clock and metabolic gene expression, whereas metformin led to mainly high-amplitude shifted rhythms. Combination of metformin and LE led to an antagonistic effect on circadian gene expression. Although metformin and LE have an opposing effect on circadian gene expression and on the cellular energy status, they both lead to AMPK activation.

Original languageAmerican English
Pages (from-to)151-161
Number of pages11
JournalInternational Journal of Biochemistry and Cell Biology
StatePublished - Aug 2014

Bibliographical note

Funding Information:
This study was supported by the The Israel Science Foundation ( 1044/12 ). The authors declare no competing financial interests in relation to the work.


  • C2C12 myotubes
  • Circadian rhythms
  • Lipid emulsion
  • Metabolism
  • Metformin


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