Mice become Obese WITHOUT Consuming Any More Calories

barb1241

BS for humans. At least for this human who has lost 70 lbs eating my dinner at 7 pm and a snack at 11:30 pm. Oh, and I don't eat breakfast until 1 in the afternoon. Maybe the mice should copy me.

TDGee

When the **** did mice start learning to tell time? And exactly where do they get their watches? Last I heard that the last time mice had anything to do with a timepiece, it turned out badly for them, Hickory, Deekory, Dock.

bcampbell54

Were the mice eating back their exercise calories?
And did they count coffee in their water glass count?

RobynC79

what is an unnatural time for a mouse? I'm hungry, I'm gonna nom on something!

Mice, like rats, are primarily nocturnal. So a mouse will naturally eat at night and sleep during the day. The study states that the mice with messed up internal clocks ate during the day, when they should have been sleeping. So there really is an unnatural time for a mouse to eat.

We metabolize differently

How? Can you give some concrete examples?

I'm trying to find actual research on this but my understanding is that de novo lipogensis occurs much more readily in rats vs humans.

I believe these are relevant but I'll be brutally honest in that I just skimmed these but this should show differences in lipogenesis between species:

http://www.sciencedirect.com/science/article/pii/002604957190059X
http://www.jlr.org/content/44/11/2127.full.pdf

EDIT: I don't have the full text for the top one unfortunately.

So both of those refer to rats only, with no mention of mice. In mice, it is known that the cholesterol metabolism is different, presumably because mice are almost exclusively herbivorous, in contrast to humans (and rats), so dietary cholesterol is much lower in mice.

In both of the studies you cite, (BTW, I do have a full-text of the first, if you are interested I would be happy to send it to you) the focus is in lipogenesis that occurs in adipose tissues. In humans this is a smaller proportion than in rats, because most FAM occurs in the liver in humans. That study is from 1971, and it seems since then there is a better understanding of the larger role of the liver in humans in FAM. I cannot say that overall, lipogenesis occurs more readily in rats, because the studies only examine rates in one tissue type.

In the study that is the topic of this thread, the conclusion is that a change in a gene in fat cells has substantial downstream effects, but not that adipose tissues changed their own contributions to lipogenesis (although this may be occurring, but I can't tell from the study).

So there are differences in rats and humans in where fats are primarily metabolised, but perhaps not in overall rates acroos various organs. Also, these are mice, not rats, which have their own differences from humans, but are generally a very good genetci models for humans.

RobynC79

For those of you asking how the metabolism of a human and rodent differ-Rats are carb burners; they consume and rapidly use large amounts of carbohydrates to survive. Humans are fat burners, meaning we don’t need carbs constantly since our body can easily store energy in the form of fat. Therefore, something that prevents obesity and activates lipid metabolism in rodents will have different effects in humans, unless those rodents’ metabolisms have been altered to mimic those of humans.

This is false. Both humans and rats (and again, this study used MICE) store energy both as fat and glycogen, and utilise both in very similar ways. Rats have an omnivorous diet very much like humans, will consume both fat and carbohydrate readily, and will gain weight on a caloric excess of either. Humans and rats both deplete free glucose, muscle gylcogen and stored fats during exertion, and all are converted to glucose for use as cellular energy. The terms 'carb burners' and 'fat burners' are not scientifically valid - all mammals burn a combination of both fuel types (if we assume 'carb burning' refers to glycogen).

UsedToBeHusky

For those of you asking how the metabolism of a human and rodent differ-Rats are carb burners; they consume and rapidly use large amounts of carbohydrates to survive. Humans are fat burners, meaning we don’t need carbs constantly since our body can easily store energy in the form of fat. Therefore, something that prevents obesity and activates lipid metabolism in rodents will have different effects in humans, unless those rodents’ metabolisms have been altered to mimic those of humans.

I don't know if I agree with your 'carb-burning vs fat-burning' theory, but the main difference and problem that I see with this study is that mice and humans have a different biological clock. I made the mistake earier saying that mice weren't nocturnal... but they are. The point I was trying to get at with that was that the mice were being fed at time when they are used to being inactive. As someone else pointed out, we have the will to defy our own natural instincts. We can choose to be active when we choose too. Therefore, I could see why feed-timing would have a different effect on mice than humans. But usually, scientists don't expect to prove definitively that what happens to mice also happens to humans, but more that if it the effect in mice exists, then to some degree the effect could also occur in humans. One controlled study is never considered to be the end of all that is relevant to the topic. Now that the controlled study has proven that the effect could exist. It is up to correlative studies with human subjects to investigate the occurrence to further determine if and how frequently the effect occurs in humans. This is generally the process for information becoming accepted as fact. Either controlled studies instigate correlative studies... or vice versa. Once enough reputable scientist come to a consensus, then feed-timing could become relevant to how obesity occurs, but again, it is not a direct cause and the resultant physiological reaction that it creates could be countered just by cooking with olive oil, occassionally eating some fish, and enjoying some yummy peanut butter at will.

SideSteel

what is an unnatural time for a mouse? I'm hungry, I'm gonna nom on something!

Mice, like rats, are primarily nocturnal. So a mouse will naturally eat at night and sleep during the day. The study states that the mice with messed up internal clocks ate during the day, when they should have been sleeping. So there really is an unnatural time for a mouse to eat.

We metabolize differently

How? Can you give some concrete examples?

I'm trying to find actual research on this but my understanding is that de novo lipogensis occurs much more readily in rats vs humans.

I believe these are relevant but I'll be brutally honest in that I just skimmed these but this should show differences in lipogenesis between species:

http://www.sciencedirect.com/science/article/pii/002604957190059X
http://www.jlr.org/content/44/11/2127.full.pdf

EDIT: I don't have the full text for the top one unfortunately.

So both of those refer to rats only, with no mention of mice. In mice, it is known that the cholesterol metabolism is different, presumably because mice are almost exclusively herbivorous, in contrast to humans (and rats), so dietary cholesterol is much lower in mice.

In both of the studies you cite, (BTW, I do have a full-text of the first, if you are interested I would be happy to send it to you) the focus is in lipogenesis that occurs in adipose tissues. In humans this is a smaller proportion than in rats, because most FAM occurs in the liver in humans. That study is from 1971, and it seems since then there is a better understanding of the larger role of the liver in humans in FAM. I cannot say that overall, lipogenesis occurs more readily in rats, because the studies only examine rates in one tissue type.

In the study that is the topic of this thread, the conclusion is that a change in a gene in fat cells has substantial downstream effects, but not that adipose tissues changed their own contributions to lipogenesis (although this may be occurring, but I can't tell from the study).

So there are differences in rats and humans in where fats are primarily metabolised, but perhaps not in overall rates acroos various organs. Also, these are mice, not rats, which have their own differences from humans, but are generally a very good genetci models for humans.

Sorry, never even made the connection that the original study was on mice and I linked you rat studies. Oops

BogQueen1

I'm sorry, perhaps my reading comprehension skills are low tonight, but the very first line of that article states "shows that deletion of the clock gene Arntl, also known as Bmal1, in fat cells, causes mice to become obese, with a shift in the timing of when this nocturnal species normally eats" Yes I copy pasted that. They deleted a gene AND shifted timing? How does that apply to us at all?

amandammmq

The mice must have eaten at 46:98 o'clock. <

---

an unnatural time.

SideSteel

How does that apply to us at all?

^ This would be the key question and this is also why it's important not to take the findings of a study and draw them out of context.

AnvilHead

How does that apply to us at all?

^ This would be the key question and this is also why it's important not to take the findings of a study and draw them out of context.

...especially when there are plenty of studies and empirical evidence which confirm the validity of energy balance (caloric deficit) in the role of weight loss in actual human beings.

RobynC79

I'm sorry, perhaps my reading comprehension skills are low tonight, but the very first line of that article states "shows that deletion of the clock gene Arntl, also known as Bmal1, in fat cells, causes mice to become obese, with a shift in the timing of when this nocturnal species normally eats" Yes I copy pasted that. They deleted a gene AND shifted timing? How does that apply to us at all?

No, it means that deleting that gene resulted in the shifted eating times. The timing change was a consequence of the knockout, not an additional treatment.

For the question 'how does this apply to us at all', I think it's important to define the utility of knockout studies. Removing a gene is designed to reveal causality of that gene in what may be a very complicated, multifaceted physiological process. The authors wanted to show that this gene is involved in the normal daily regulation of appetite. By selectively removing it (and in this case, only in one specific tissue type), what they reveal is that 1. This exact gene is important, on it's own, for regulating this process, and 2. That the action of this particular gene in this particular tissue type, is important.

So now we know something about how appetite is regulated at the genetic level, which is potentially important for treating appetite dysregulation, and understanding how complex neurophysiological processes such as 'feeling hungry' work in a whole body.

Genetic studies are vital for showing how various gene products interact with each other. A knockout mouse is abnormal, yes, but it is abnormal in a very controlled, very revealing way.

shrinker19

Great research article. Thanks Sven.

LiftAllThePizzas

The mice didn't eat more calories, but how much was their activity changed by the disruption of their normal behavior patterns?

I know if I'm sleep-deprived, I'm not running and jumping and bouncing off the walls all day burning calories like they're going out of style. Instead I'm basically doing as little as possible and moving as little as possible.

I can eat 2500 calories a day right now and lose or maintain my weight, and I could stay at 2500 and make myself obese "WITHOUT consuming any more calories" by turning into a zombie couch potato.

erinsueburns

BS for humans. At least for this human who has lost 70 lbs eating my dinner at 7 pm and a snack at 11:30 pm. Oh, and I don't eat breakfast until 1 in the afternoon. Maybe the mice should copy me.

I think it may be more fair to say, bs for you (well and me too), when applying simplified strategies and comparisons to this study. I think one of the difficulties and large variance of anecdotal "data" among real humans, is because the definition of "unnatural" times in humans is often unclear. There it's some pretty compelling evidence that in humans there is a strong genetic component to the spectrum of larks and owls all the way to the disorders on either side of the spectrum. So for someone like me, whose "natural" bedtime is early in the A.M and "natural" wake up time is after noon (diagnosed delayed circadian sleep disorder), where does that put my "unnatural" time for me to eat? The science isn't clear really, It just muddies the waters to a greater extent. Personally, I finally decided based on long trial and food logging and diary tracking (notes like sure this felt well, poorly, threw up etc), that it is "unnatural" for ME to eat during the times that it is "unnatural" for me to be awake, even if I'm up anyway as I must be for my job.

And that is one way humans are very different than mice. We are not all uniformly diurnal, some of us are nocturnal by biology.

So my question I guess (looking for anecdata is fun!) is for those who have been successful weight loss/maintain night eaters, and unsuccessful ones. Where do you fall on the lark night owl scale?

ladywendolyn

The mice got fat because they were sleeping all day due to being up at such unnatural times )

slkehl

For those of you asking how the metabolism of a human and rodent differ-Rats are carb burners; they consume and rapidly use large amounts of carbohydrates to survive. Humans are fat burners, meaning we don’t need carbs constantly since our body can easily store energy in the form of fat. Therefore, something that prevents obesity and activates lipid metabolism in rodents will have different effects in humans, unless those rodents’ metabolisms have been altered to mimic those of humans.

This is false. Both humans and rats (and again, this study used MICE) store energy both as fat and glycogen, and utilise both in very similar ways. Rats have an omnivorous diet very much like humans, will consume both fat and carbohydrate readily, and will gain weight on a caloric excess of either. Humans and rats both deplete free glucose, muscle gylcogen and stored fats during exertion, and all are converted to glucose for use as cellular energy. The terms 'carb burners' and 'fat burners' are not scientifically valid - all mammals burn a combination of both fuel types (if we assume 'carb burning' refers to glycogen).

I realize that all mammals burn a combination of both fuel types, but I'm under the impression that at a normal weight, a mouse will utilize and constantly replace glycogen stores more often than a human, who will tend to delve into fat stores more often. "Carb-burners" and "fat-burners" were simply given to us in class as a way to remember that difference. It's been a while since I learned about the specific differences, but I DO know that studies on mice are exploratory-they can give potentially important insight into potential issues but can't give reliable conclusions on their own.

Pixi_Rex

So do they like time travel or something? That's the only thing I can think of that would be an 'unnatural time' .

jenilla1

Mice eating at unnatural times? I'm pretty sure mice in the wild don't keep a schedule - they are mostly nocturnal, but I've seen them moving around in the barn in the daytime plenty of times. (Maybe I woke them?) My unnatural mouse ate at different times of the day or night depending on hunger I guess. She wasn't obese. (Or maybe she was - LOL) They just eat what they find when they find it and store what they don't eat for later. What other "unnatural" things were the mice subjected to in the lab? Just being in a lab is a bit unnatural, isn't it?

ETA: Not sure this mouse study translates to humans. At least not to all of us. I eat most of my cals in the evening and I have never been overweight.

ashleab37

Many studies show that there is a correlation with obesity related disease and night eating and night shift workers. The mechanism is not really known in humans but scientists think it could be the same as what is observed in these mice.

I gained 30kg while working night shift.
Not because it makes any difference at all what time of day you eat, but because it became TOO EASY to overeat.
Wake up 4pm
Eat dinner with family at 5.30pm - MEAL 1
Get to work at 7pm
Eat dinner at work at 8pm - MEAL 2
Snack on a large bag of chips, a block of chocolate, and a 2L bottle of coke (3000 calories total)
At around 2am, colleague would go to hungry jacks/mcdonalds/kfc (and of course it would be rude to say no to the offer ) - ANOTHER MEAL
On the way home at 7am, McDonalds would tempt me and I'd get two sausage and egg mcmuffin meals.

I was gaining weight on night shift because I was eating upwards of 6000 calories a day. It sounds disgusting, I know, but its just TOO EASY. Most people who work night shift eat more/worse than people who work standard shifts.