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When you eat, might be just as important as what you eat, according to new research from the Salk Institute.

May 17, 2012 1:17 p.m.


Dr. Sanchidananda, lead author of study at Salk Institute for Biological Studies

Related Story: Salk Study May Offer Drug-Free Intervention To Prevent Obesity


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CAVANAUGH: Which is KPBS Midday Edition. I'm Maureen Cavanaugh. A new study for scientists at the Salk institute for biological studies may make you think twice about having a late-night snack. Studies with mice indicate that the same amount of fat and calories is metabolized differently according to when it's eaten. Joining me is my guest, doctor Sachin Panda, associate professor in the regulatory biology laboratory at Salk. We spoke to you last year when your research at Salk led to the discovery of a gene that's responsible for waking us up every day. This new research investigates the body's natural rhythms, but focuses instead on eating. I thought when we ate is always more important than when. Is that wrong?

PANDA: That's partly right. Actually, most of our currently recommendation, lifestyle recommendation to prevent obesity and diabetes is based on this simple formula that a calorie is a calorie is a calorie. And when it goes into our body, it either has to be stored as fat or spent in physical activity. Based on my research and the circadian clock, now we know that every part of our body has a clock. So just like we cannot do complex math in the middle of the night, our brain cannot do that, whereas in the middle of the day, we can do much more efficiently, our liver and gut can digest that food and burn up that fat much better if weate in the day night, and past a few hours of night. And that was our hypothesis. Then I thought well, we can't start testing it in humans, so we started testing it in mice.

CAVANAUGH: You did your research with mice. Did you feed them all the same thing?

PANDA: Yes, so it was a very simple experiment. We just take two groups of mice, they had the same genes, just normal mice, male mice, comparable to in their early teen years, and we gave them fatty food, which is equivalent to you can imagine us eating ice cream, chips all the time. So these two groups of mice get exactly the same number of calories every single day. One group gets to eat whenever they want, and they will eat all day and night. And then the second group gets to eat the same amount of calorie, but they eat only for eight hours. And we did this for almost 100 day, three month, which is a long period of time in a mouse's life. And at the end of three month, we see that mice who are eating randomly whenever they want, they become obese, the body mass around 40% is fat, they have high cholesterol, high blood sugar, high insulin. The liver shows signs of damage. And they cannot perform very well in exercise tests. And what is really surprising was the second group of mice, which were eating only for eight hours, they were eating all their food in those eight hours. And this group of mice did not become obese. Only 10% of their body weight was fat. And just normal blood glucose, normal cholesterol level, and normal insulin level, and most surprisingly, if we put them on an exercise test, they performed much better than mice that were eating healthy food.

CAVANAUGH: And you deliberately fed these mice a very bad mouse diet.



CAVANAUGH: The equivalent to chips and mouse ice cream. Why did you decide to feed them that kind of a diet?

PANDA: Because we think that if we start with a very bad diet, then we can see the maximum difference. And if with the bad diet we can protect the mice from all these bad diseases, then we can imagine that even with a good diet, you might get a beneficial effect.


PANDA: So we had two groups of mice which were eating healthy food, and just like this, one was eating whenever they want, and the other group was eating only for eight hours. You cannot make mice more healthy because they are eating healthy food. But what was interesting was the mice that were eating only for eight hours, even a healthy diet, their liver function was much better than mice that were just eating whenever they want. And their performed much better on exercise tests. So that's very interesting because one would ask, well, are the mice were actually fasting for 12-16 hours every day, they must be really tired, maybe lethargic. So they may not perform well on exercise. What I think what happened was just like after gorging a lot of food at night in the morning, we have the food fatigue, food hangover.

CAVANAUGH: Yeah, right

PANDA: That's what they're not eating. They don't have the food hangover the next day. So they feel much better, they perform much better on exercise. And that's why we're very excited about this.

CAVANAUGH: How does the mouse time cycle, the metabolic cycle that the mouse goes through, and the number of hours the mice were kept away from food, how does that translate into a human metabolic cycle?

PANDA: Yes, so we humans for hundreds of thousands of years, we ate mostly during the daytime, and only in the last 100 years or so we started to eat a little bit at during nighttime, and it became worse in the last 30-40 years when our social life actually starts after sunset, after we come back from work, and we continue to eat late into the night. Mice are nocturnal. So what we expect is we can potentially translate it into humans, so in humans who eat mostly during the daytime and have an early dinner, and have no snacking, they might show a similar improvement in their blood sugar level, cholesterol level:

CAVANAUGH: Now, lately, the advice to people who want to lose weight, maintain a healthy weight, is to eat smaller meals through the day, separated by 2-3 hours, and keep that calorie level in line with what's reasonable for your goals. But that -- in a way, to stock the fire so to speak, keep your metabolism from shutting down. What does your research say to that?

PANDA: Actually in this, in our study, the mice actually keep eating for those eight hours. They are not stopping. They are eating in small bites throughout eight hours. And so that we should eat small meals every 2-3 hours, yes, that's true. But then we should stop!


PANDA: We just can't keep eating till we go to bed at midnight. I think that's also perfectly fine. What we see is very interesting. When we fast, or when these mice are fasting for 12-16 hours, during that time, after 5-six hours of fasting, they turn on their fat burning process. So in every night for 6-seven hours, they are actually burning foot very nicely. Another thing is --

CAVANAUGH: So they're burningly fat while they're sleeping? ?

PANDA: Yeah, so what happens is you would ask, what is happening in these mice? And three or four things that we really care about. Blood glucose, fat, and cholesterol. So what happens is, when we are sleeping, and when we are fasting, our liver actually makes glucose, and sends it to the brain. And the liver should not make glucose when we're eating. But when we eat more frequently, and when mice eat more frequently, the liver clock gets confused, when to make glucose and when not to make. And the liver just continues to make glucose. And we also continue to eat. So that increases in blood sugar levels. And when we get back to that feeding/fasting cycle, then the liver knows when to stop making glucose. So essentially our liver makes less glucose, and the level goes down.

CAVANAUGH: When you're talking about fasting, you're talking about it in a slightly different way. We normally think about fasting as perhaps refraining from hard food, any kind of real food for a day, perhaps even two days. What you're talking about is a regular time of fasting each day, like for maybe half a day, right?

PANDA: Yeah. So this is a very natural way of how our bodies work. Our body is wired not to see any food throughout the night. And throughout the day, humans actually ate throughout the day in small snacks, that's what we are talking about.

CAVANAUGH: A lot of people do it the other way around though.


CAVANAUGH: They don't eat anything during the day, then when they get home, they eat everything in sight. That's not going to work?

PANDA: Yeah, so what happens is, we are always told you start with a good breakfast. So we start with a breakfast, and throughout the day, although we are not eating, we keep munching some small snacks here and there, and then juice or drinks. And then in evening, we start our real eating because eating is part of our social life; part of entertainment. So we keep eating and drinking through the night. So the number of hours we eat has gone up from 10-12 hours to almost 16-18 hours am the


PANDA: So that's what we mean. The number of hours we eat, when it goes up, then a lot of bad things happen.

CAVANAUGH: In some cultures, it reminds me in Europe, the time that they eat their main dinner, are you know, will be about 8:00, 9:00 in the evening. Are they doing that wrong then?

PANDA: Well, the thing is, we actually don't have much data on when people eat. And we kind of remember, okay, they are actually eating late into the night. But we don't know when do they start their breakfast?


PANDA: Are they actually starting their breakfast late? So there are many questions that are -- that are now coming up with this study, and the first is when do we actually eat? And we don't have a good record of when we eat.

CAVANAUGH: That's -- yeah, so more research needs to be done to try to get all of those different -- I'm thinking too, are people who are on different workshifts.


CAVANAUGH: Perhaps they get home at 10:00 at night, and that's when they have their dinner. Would you, based on what you know now, advise people to try to eat a little bit earlier, even if they are on a schedule like that?

PANDA: Yeah, so based on this research, what we think is whatever our body is designed for is best to do that way. So for example, we are designed to eat in the daytime, so that might be the best thing. But I agree, some shift workers who are starting very early in the morning or working till late at night, I think for them, it would be very important to stick to the same schedule. Because what happens is, when we get the times off, then we go back to our daytime schedule, and just like when you travel from east coast to west coast or vice versa, your sleep cycle gets disturbed, your liver clock also gets confused when you do that. And I think that leads to over a long period of time, that can lead to metabolic disease. So if you stay on the same schedule, try to say on the same schedule, that is more important.

CAVANAUGH: What do you think will be the takeaway for people who are trying to control their weight or perhaps even more serious problems, diabetes, in looking at the results of your research?

PANDA: So right now, it would be really hard for me to recommend anything for humans because the study was done in mice. But historically, most of the lifestyle interventions started in mice and translated very well to humans. So I would guess that looking at how we eat, we actually start our breakfast with a very healthy food, most of us, and as the day progresses, we tend to eat more and more unhealthy food. And if you think about what we eat after dinner, it's mostly unhealthy food. So if we just come up with this idea that, well, let's eat only for 10-12 hours, and start counting from breakfast, then what'll happen is at the end of the day, those unhealthy foods that we eat, which constitute around 20-30% of our caloric intake, that will go away from our diet. So it will reduce some intake. And second, you will get the benefits of fasting. During this overnight fasting, another thing that happens is we break down our cholesterol. And that goes and turns on what is now known as brown fat, and is it literally burns your calories. It takes this fat, breaks it down to heat, and the heat comes out of our body. So that process will start. So I think we are very hopeful that we can translate it into humans. We are actually very shortly going to start a human study. We are very excited. We have raised some money from research foundations and federal government and then start the study in humans.

CAVANAUGH: This has been fascinating. Doctor Sachin Panda of the regulatory biology laboratory at Salk. Thank you so much for coming in and talking with us.

PANDA: Thank you, Maureen.