Off the Clock: From Circadian Disruption to Metabolic Disease

Int J Mol Sci. 2019 Mar 30;20(7):1597. doi: 10.3390/ijms20071597.


Circadian timekeeping allows appropriate temporal regulation of an organism's internal metabolism to anticipate and respond to recurrent daily changes in the environment. Evidence from animal genetic models and from humans under circadian misalignment (such as shift work or jet lag) shows that disruption of circadian rhythms contributes to the development of obesity and metabolic disease. Inappropriate timing of food intake and high-fat feeding also lead to disruptions of the temporal coordination of metabolism and physiology and subsequently promote its pathogenesis. This review illustrates the impact of genetically or environmentally induced molecular clock disruption (at the level of the brain and peripheral tissues) and the interplay between the circadian system and metabolic processes. Here, we discuss some mechanisms responsible for diet-induced circadian desynchrony and consider the impact of nutritional cues in inter-organ communication, with a particular focus on the communication between peripheral organs and brain. Finally, we discuss the relay of environmental information by signal-dependent transcription factors to adjust the timing of gene oscillations. Collectively, a better knowledge of the mechanisms by which the circadian clock function can be compromised will lead to novel preventive and therapeutic strategies for obesity and other metabolic disorders arising from circadian desynchrony.

Keywords: adipose tissue; circadian rhythm; high-fat diet; metabolism; molecular clock; nutrients; obesity; suprachiasmatic nucleus.

Publication types

  • Review

MeSH terms

  • Animals
  • Circadian Clocks*
  • Circadian Rhythm Signaling Peptides and Proteins / genetics
  • Circadian Rhythm Signaling Peptides and Proteins / metabolism
  • Energy Metabolism
  • Humans
  • Metabolic Diseases / metabolism*
  • Metabolic Diseases / physiopathology


  • Circadian Rhythm Signaling Peptides and Proteins