Researchers at the University of California, Irvine have revealed a fascinating connection between cellular metabolism and the circadian rhythm — commonly known as the biological clock. Conducted in the laboratory of Dr. Paolo Sassone-Corsi, one of the world’s leading researchers on circadian genetics, a recent project examined the effects of a high-fat diet on the expression of genes responsible for unintended circadian oscillation (weird biological rhythms). The study, “Reprogramming of the Circadian Clock by Nutritional Challenge,” was published in the journal Cell in November of 2013.
But first, what exactly is the circadian rhythm? For the typical college student, it’s certainly something that many of our priorities and schedules disagree with us on. However, for the ordinary sentient organism, the circadian rhythm is the daily cycle of biological events and activities that typically occur in a predictable fashion. In human beings, the circadian rhythm is responsible for processes such as the sleeping and waking cycle; it may cause one to feel keen and alert at one point of the day and more lethargic at another. For the researchers at UC Irvine, circadian rhythm is an intricate timepiece hinged upon a complex, dynamic set of genes that respond, interestingly enough, to dietary composition.
The study itself was conducted on wild-type rodents. The test subjects were divided into two distinct groups: those fed a diet of “normal chow” [NC] (the regular, unadulterated rodent food) and those fed a “high-fat” [HF] diet, representative of a traditional high-fat human diet. The team chose to closely examine the liver tissue of the rodents, which allowed them to determine the overarching effects of the diet on their circadian rhythms.
“The liver is a beautiful organ to look at because it has a very powerful intrinsic clock, and it’s composed of almost all homogeneous tissue,” Dr. Sassone-Corsi said. “This allows a nice look at the biochemistry … it allows the direct study of the effect of nutrition on metabolism.”
The research team determined that the mice fed a consistent diet of normal chow have a certain set of circadian genes activated. When the mice are placed on the high-fat meal plan however, an entirely different set of genes are switched on. This causes a major shift away from the organism’s original circadian rhythm.
Dr. Pierre Baldi is a key member of the study’s bio-informatics team, responsible for the collection and analysis of highly complex genetic data.
“Roughly 10 percent of an organism’s circadian genome is oscillating in a given cell,” Dr. Baldi said. “The 10 percent that is oscillating is different from cell to cell, tissue to tissue, organ to organ … A high-fat diet disrupts normal oscillation and creates new rhythms altogether.”
Lead author of the study, Kristin Eckel-Mahan, elaborated on some of the specific biochemical alterations.
“… A high-fat diet resulted in the cessation of many of the existing circadian oscillations within the cell’s metabolome and transcriptome,” Eckel-Mahan said. “This is attributable in part to the aberrant chromatin recruitment of the CLOCK and BMAL1 proteins, which are two transcription factors essential for cellular rhythmicity … A high-fat diet both blocks existing oscillations within the hepatic [liver] clock while inducing new oscillations where and when they would not take place under normal conditions.”
The research team was able to determine that this drastic shift in biochemical rhythm can happen when an organism consumes a high-fat diet over a very short period of time (Christmas break, anyone?). Luckily however, reverting back to a controlled lower-fat diet allows the organism to return to its original bio-clock.
“You can have a high-fat diet for five days, and you can re-program your clock in this time … In the study, if we take an obese subject on a high-fat diet and put them back on a diet of normal chow, their clock will revert to a normal circadian rhythm … this is encouraging because you have not locked the system into something irreversible,” Dr. Sassone-Corsi said.
The question that that research teams will seek to answer in the future is how different diets, not just a typical high-fat diet, can impact an organism’s circadian rhythm. The Atkins, Paleo, Vegan and Mediterranean diets are prime examples of popular dietary paradigms employed today, and each one may have its own unique effect on gene expression and circadian rhythm.
Once again, research reminds us that our dietary patterns and lifestyle choices dictate both our physical status and our lives in more ways than previously imagined.
