Eating as a more powerful clock-setting mechanism than light in some organs | Satchin Panda
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Humans and many other organisms have a transcription factor called CLOCK, which affects both the persistence and period of circadian rhythms. CLOCK is widely distributed in the human body, and it regulates the expression of genes in response to external cues like light and food. Altering those cues from those normal day-night patterns can have negative effects on our metabolism, especially in organs like the liver. In this clip, Dr. Satchin Panda describes CLOCK's varied response to light and food and how those responses affect metabolism.
-Rhonda: So let's talk a little bit about how food regulates...
[Stachin] Yeah.
Rhonda: ...these clocks and these different tissues.
Satchin: Yes. A few years ago, we started looking at which genes are regulated by CLOCK in different organs. So if we look at liver, there are somewhere between 3000 to 5000 genes that are turned on at certain time of the day or night. And so that's...
Rhonda: A lot of genes.
Satchin: A lot of genes. So, that's almost 30% of expressed genome or whatever. Um, but what is interesting is, we said, "Well…" We did a very simple experiment where these are done in mice. so the night-eating mice...mice usually eat during the night time, that we asked, "Well, there is a master regulator in the brain that's telling the rest of the body when the timing is, when it's day or night, and let's give mice food in the middle of the day, just like the shift workers work in the night time, they eat. If we do that, then what happens to the liver? That all liver genes, that cycle, that take the cue from light-dark cycle or from the food?" Because we have these two groups of mice, both groups of mice are in the same light-dark cycle. One group it's doing day, one group it's doing night. The liver takes cue from light-dark cycle then all cycling gene should be identical in two groups. If the liver clocks take cue from eating time, then the day-fed animals will have a different clock than the night-fed animals.
And that's exactly what we found, that even though the light-dark cycle are the same for both animals, the liver clock responds to when the mice ate. So the day-fed animals had the same 3000 genes cycling. The night fed animals had the same 3000 genes cycling. But now the genes that are turning on during daytime in the day-fed animals, now they turn on at nighttime in the night-fed animals.
So that means the time when we eat tells our liver clock when to turn on the genes and when to turn off. The light has very little impact. We cannot say no impact, very little impact on the cycling genes in the liver. So that experiment has been replicated now, and what we are learning is almost every organ in our periphery outside the brain kind of follows when we eat.
So then what becomes very important in the daily life is the first sight of bright light and the first bite of food. Those two determine how our body clocks work.
The body’s 24-hour cycles of biological, hormonal, and behavioral patterns. Circadian rhythms modulate a wide array of physiological processes, including the body’s production of hormones that regulate sleep, hunger, metabolism, and others, ultimately influencing body weight, performance, and susceptibility to disease. As much as 80 percent of gene expression in mammals is under circadian control, including genes in the brain, liver, and muscle.[1] Consequently, circadian rhythmicity may have profound implications for human healthspan.
- ^ Dkhissi-Benyahya, Ouria; Chang, Max; Mure, Ludovic S; Benegiamo, Giorgia; Panda, Satchidananda; Le, Hiep D., et al. (2018). Diurnal Transcriptome Atlas Of A Primate Across Major Neural And Peripheral Tissues Science 359, 6381.
A gene encoding a transcription factor (CLOCK) that affects both the persistence and period of circadian rhythms. CLOCK functions as an essential activator of downstream elements in the pathway critical to the generation of circadian rhythms. In humans, polymorphisms in the CLOCK gene have been associated with increased insomnia, weight loss difficulty, and recurrence of major depressive episodes in patients with bipolar disorder.
A person who works on a schedule outside the traditional 9 AM – 5 PM day. Work can involve evening or night shifts, early morning shifts, and rotating shifts. Many industries rely heavily on shift work, and millions of people work in jobs that require shift schedules.
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