Differential Effect of Fructose in the Presence or Absence of Fatty Acids on Circadian Metabolism in Hepatocytes

Shani Tsameret, Nava Chapnik, Oren Froy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


We aimed to explore whether fructose in the absence or presence of fatty acids modulates circadian metabolism in AML-12 hepatocytes. Fructose treatment under steatosis conditions (FruFA) led to fat synthesis resulting in increased triglycerides and cholesterol content. Fructose led to reduced activity of the AMPK and mTOR-signaling pathway. However, FruFA treatment led to inhibition of the AMPK signaling pathway but activation of the mTOR pathway. Fructose also increased the expression of inflammatory markers, whereas the addition of fatty acids dampened their circadian expression. At the clock level, fructose or FruFA altered the expression of the core clock. More specifically, fructose led to altered expression of the BMAL1-RORα-REV-ERBα axis, together with reduced phosphorylated BMAL1 levels. In conclusion, our results show that hepatocytes treated with fructose respond differently if fatty acids are present, leading to a differential effect on metabolism and circadian rhythms. This is achieved by modulating BMAL1 activity and expression.

Original languageAmerican English
Article number138
Issue number2
StatePublished - Feb 2023

Bibliographical note

Publisher Copyright:
© 2023 by the authors.


  • circadian rhythms
  • clock
  • fatty acids
  • fructose
  • glucose
  • metabolism
  • oscillation


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