The study, published in Cell, used high-throughput profiling of the liver metabolome and transcriptome to test the effects of a high-fat dietary challenge on metabolism - finding that the high-fat diet (HFD) challenge altered the molecular mechanism that control the internal body clock which regulates metabolic functions in the liver.
Led by Professor Paolo Sassone-Corsi from the University of California-Irvine, the team suggested that such disruption of these circadian rhythms could contribute to metabolic distress and diseases including diabetes, obesity and high blood pressure.
"HFD induces transcriptional reprogramming within the clock that reorganizes the relationships between the circadian transcriptome and the metabolome," wrote the research team.
"Nutrients have powerful effects on the cellular clock, revealing its intrinsic plasticity," they explained. "These effects consist not only of the abrogation of pre-existing rhythms but the genesis of rhythms where they do not normally exist. This induction is rapid and does not require the onset of obesity."
Reversing the rhythm?
In addition to finding that a high-fat diet has a negative impact on metabolism and circadian rhythm, Sassone-Corsi and his team also found that returning to a balanced, low-fat diet normalised the rhythms.
"The reversible nature of these effects gives hope for novel nutritional and pharmaceutical strategies," commented the research team.
The team reported that the high-fat diet reprograms the liver clock through two main mechanisms: one which blocks normal cycles by impeding the clock regulator genes known as CLOCK:BMAL1, while another initiates a new program of oscillations by activating genes that normally do not oscillate. This occurs principally through a factor called PPAR-gamma, the team said.
Sassone-Corsi commented that it is noteworthy that this reprogramming takes place independently of obesity; rather, it's solely dependent upon caloric intake – showing the remarkable adaptability of the circadian clock.
The team now plan to extend their research to assess the effects of high-fat diet on other body tissues and functions, including muscle, fat, the brain and blood plasma.
Volume 155, Issue 7 , Pages 1464–1478, doi: 10.1016/j.cell.2013.11.034
"Reprogramming of the Circadian Clock by Nutritional Challenge"
Authors: Kristin L. Eckel-Mahan, Vishal R. Patel, Sara de Mateo, et al