Wednesday, February 27, 2013

Your Brain on Potato Chips

Or, more accurately, a rat's brain on potato chips.  Last week, PLoS One published a very interesting paper by Dr. Tobias Hoch and colleagues on what happens in a rat's brain when it is exposed to a highly palatable/rewarding food (1).  Rats, like humans, overconsume highly palatable foods even when they're sated on less palatable foods (2), and feeding rats a variety of palatable human junk foods is one of the most effective ways to fatten them (3).  Since the brain directs all behaviors, food consumption is an expression of brain activity patterns.  So what is the brain activity pattern that leads to the overconsumption of a highly palatable and rewarding food?

Researchers have already uncovered a large amount of information about this process.  In short, it centers around the activation of the mesolimbic reward system, including but not limited to the ventral tegmental area (VTA; a major source of dopamine), the nucleus accumbens (NAc), the dorsal striatum, and the lateral hypothalamus (LH; specifically orexin neurons).  Chemically manipulating the nucleus accumbens or lateral hypothalamus causes voracious feeding in sated rats, replicating the natural behavior that is observed in rats exposed to highly palatable food (4, 5).  This is the system that motivates you to seek things that are desirable, including certain foods.

Here's a schematic of the rat brain showing some of the relevant structures, as well as dopamine pathways coming from the VTA and the substantia nigra (image reproduced from the lab page of Dr. Jeremy Clark here at UW; 6).  Many other connections and neurotransmitter systems are not pictured**.


Most of the approaches used in the past to study reward-based feeding have been invasive or involved chemical manipulations that complicate the interpretation of results as they pertain to natural behavior.  Enter the recent study.  Dr. Hoch and colleagues used a twist on an interesting technique called MEMRI*, which allowed them to monitor cumulative neuron activity over a 7-day period in freely behaving rats.  Rats were divided into two groups, and each received a different diet:
  1. Normal rat chow plus crushed rat chow.
  2. Normal rat chow plus crushed potato chips.  Score!
Rats, like humans, love potato chips, and as expected group #2 group ate a lot of chips over the 7-day period, significantly increasing total calorie intake.

The changes in brain activity were striking.  Here's a cool image from the paper.  Regions in red showed increased activity, while regions in blue showed reduced activity:


The NAc, perhaps the most iconic reward/addiction-related structure in the brain, was strongly activated in group #2.  Other structures related to reward also lit up, including the dorsal striatum and LH.  Neuron activity in the VTA 'paradoxically' was suppressed.  This could probably be explained by someone who knows more about the VTA than I, but I do think it's worth noting that some neurons signal by firing less rather than more.

This is where the findings become even more interesting.  Group #2 experienced a decrease in the activity of brain regions that regulate energy homeostasis, including the arcuate nucleus in the hypothalamus and the nucleus tractus solitarius in the brainstem, consistent with the possibility that consumption of a hyperpalatable food may have 'shut down' the mechanisms that normally prevent excess food intake.  We can't take this line of reasoning too far, because each of these structures contains a variety of cell types doing different things, and looking at global activity patterns doesn't necessarily give us a clear idea of what's going on at the cellular level.  But it's an interesting hint nevertheless.

Also, they found changes in brain regions related to sleep and wakefulness, which is interesting given the emerging links between circadian rhythms, sleep, food intake and obesity.

Since humans have essentially the same brain structures as rats, and these structures serve similar purposes, this is probably roughly what happens in the human brain during habitual consumption of highly palatable junk food.  The reward system gets revved up, and the regions that would normally oppose food intake and body fatness may be shut down as a consequence.


* Manganese-Enhanced Magnetic Resonance Imaging.  The basic idea is that when neurons fire strongly, they take in calcium, which acts as an intracellular second messenger.  Normally, this calcium is transported out of the cell after it has done its job.  However, manganese can also get in through these channels, but it isn't efficiently exported afterward.  So if researchers experimentally increase the concentration of manganese in the brain, it accumulates in neurons in proportion to the amount each neuron has fired.  This accumulated manganese can then be detected by MRI.  MEMRI has been around for a while, but the current authors improved on it by using a gradual low-dose infusion rather than a large acute injection, which tends to make the animals sick.

** Besides dopamine, neurons in the reward system use endorphins, orexins, cannabinoids, glutamate, GABA, and other signals.  Connections between the VTA, the NAc, and the LH are central to food reward, though other areas are also important.  These connections are mediated primarily by dopamine, orexin, GABA, and glutamate signals.

24 comments:

richie said...

Can you briefly explain how hyperpalatable foods might affect circadian rhythms?

Joshua Bennett said...

Stephan, thanks for reporting cool research like this, and for doing it well. You emphasize what's uncertain or needs more testing, rather than drawing broad generalizations like many science journalists I've read. We need more of this kind of writing.

gunther gatherer said...

"Also, they found changes in brain regions related to sleep and wakefulness, which is interesting given the emerging links between circadian rhythms, sleep, food intake and obesity."

Can you explain these changes please?

What are the basic links between these rhythms and food intake? I have a friend who's rail skinny at 38 y.o. and only sleeps about 4 hours a night (no he's not taking drugs or caffeine). When I was 20, I could sleep til noon but still had a tendency to get fat even then. Now I'm much skinnier but I wake up and find I need much less sleep.

I don't understand the connection, as I've read less sleep usually means raised hunger the next day. And all the paleo go on about getting a minimum of 9 hrs sleep per day to stay lean.

Is there a basic way to understand how food intake and circadian rhythms intertwine, for non-neurology geeks like me?

anand srivastava said...

Did it cause an increase in weight?

That wasn't studied I guess.

But it could be that after an initial increase in weight, the weight might get stable. Another issue could be that the chips are fried in soyabean or corn oil.

Stephan Guyenet said...

Hi Richie and Gunther,

The short answer is that I don't know for sure, and I don't think anyone does.

However, I can speculate. Animals fed highly palatable calorie-dense foods tend to eat more during their sleep phase (in the case of rodents, this is the light phase). It could simply relate to alterations in sleep due to frequent interruptions by reward-driven feeding. Or perhaps it's an effect of overeating itself, or of the composition of the diet.

Hi Anand,

I didn't see weight reported. It was only a 7-day intervention and I think the authors would probably argue that they didn't want weight gain, which is a potential confounding variable. I have to assume they would have gained weight because their calorie intake was substantially elevated.

I agree that foods deep fried in refined seed oils (or any other oils for that matter) are unhealthy, but there's no reason to believe that brain activity patterns would have differed if a different type of fat had been used.

Gretchen said...

"this is probably roughly what happens in the human brain during habitual consumption of highly palatable junk food."

Would you expect the same during habitual consumption of highly palatable non-junk food?

ivat said...

The rats may have become a bit more hyper from eating the junk. This might affect their sleep, I should think. Kids in schools can get hyper after fixing up on junk food at break.

Michael Terry said...

Hi Stephan,

What do you think about this?

http://opinionator.blogs.nytimes.com/2013/02/27/its-the-sugar-folks/?src=me&ref=general

Especially, is the referenced study good evidence?

Stephan Guyenet said...

Hi Michael,

Bittman misunderstood the study. The study confirmed what has been well established for a long time: obesity is the main risk factor for diabetes. However, it also found that sugar was associated with diabetes risk even after controlling for obesity. In other words, both obesity and sugar consumption were associated with diabetes risk.

We have always known that there are factors besides obesity that contribute to diabetes risk, including physical inactivity and genetics. This study suggests that one of those factors is sugar consumption.

However, the study has some major methodological limitations. The FAO database it is based on was not designed to do this kind of study. It reports food supply data, not food consumption data (as pointed out by Melissa McEwen). The two are correlated but not the same. Plus the data aren't always very accurate, depending on the country. Another limitation is that this is an "ecological study", in other words it compares populations rather than individuals. In the paper, they applied some sophisticated statistical techniques to the data to minimize some of these issues, but there's no getting around the fact that the data set they used is inferior to what is typically used for prospective observational studies that compare individuals.

And it turns out that those prospective studies have not consistently found that total sugar intake predicts diabetes risk, although they do tend to find that sugar-sweetened beverage consumption predicts risk. My take is that the latest study is interesting, and it adds meaningfully to the existing evidence, but it's hardly a smoking gun.

Stephan Guyenet said...

I'll also add that sugar consumption was not associated with obesity prevalence, which is consistent with other studies.

Hi Gretchen,

I imagine there would be similarities and differences. Food quality (protein, fiber, etc.) impacts satiety factors, which impact brain activity. Satiety also impacts reward and pleasure functions (e.g. you're less interested in food when you're full).

Grinch said...

I think the evidence is clear that highly palatable foods cause people to overeat over the short term, such as one or more meals in a day. But really, how does that translate into obesity? I know that I love food and I can eat double my normal calorie intake when you put the right junk in front of me. But I always, always have an easier time eating less the next day when I do this. Because my body is to some extent, resistant to becoming obese. Now I can gain 20-30 lbs, but that's about it and my drive to overeat isn't strong enough to sustain the weight gain no matter how palatable the food is.

So is there any evidence that food reward / palatability has the ability to hinder the long-term homeostatic system enough to permanently result in obesity?

Robert said...

Dr. Guyenet,

Unfortunately, I do not think we will be able to overcome the ecological fallacy in our lifetime.

To do so will require multiple single-payer HC systems, such as in France and UK, to follow prospective national cohorts for decades all while measuring lifestyle/demographics, body fat and food consumption at each annual HC visit.

This should give us data on millions of individual people's eating habits, lifestyle habits, body fat, and metabolic health (A1c, blood lipids, etc.) and body fat/weight gain over time.

A few thousand people with FFQ's every 4 years, as in the Nurse's Health Study, is simply not enough data or accurate enough to draw conclusions about individual habits or determine what people should eat.

Despite this, nutrition scientists and journalists still seem to draw far-reaching conclusions from these weak data. Which is frustrating.

glib said...

Nothing to see here. Corporations try to create addiction, and surely your brain on chips is similar to your brain on heroin.

The question is whether their scientists should start capitalizing all the work that has been done on our brains on drugs, then test their new products to subjects that have electrodes all over the skull. The product which most closely matches the cocaine brain response is the one which hits the shelves. It will necessarily come to this, and the current studies on packaging will look incredibly lame and inoffensive.

Gretchen said...

I asked because (1) I think there's an assumption that only junk/fast food is fattening and (2) we need to explain why poor people tend to be fatter than rich people.

I gained weight without eating a lot of processed foods, unless you consider rice processed. I'm a lazy cook, so I'd cook up huge vats of rice and then reheat it with different sauces. My favorite was sesame oil and kim chee. Sometimes cheese. Sometimes meat and tomato sauce.

I also ate homemade French bread and butter. Had a garden and grew lots of my own veggies. My problem was not junk food but simple too much food, too easily prepared, eaten too often.

I find the kinds of food served at upscale restaurants (not that I often eat there) more palatable than fast food.

Jack C said...

Dr. Guyenet,

About 25% of calories in potato chips come from n-6 linoleic acid (LA), the precursor to arachidonic acid (AA)which is the backbone of endocannibinoids which are mild opioids that activate the came receptors in the gut, brain and liver that are activated by marijuana. Hence LA, like marijuana, causes the munchies and induces obesity.

A recent study on the subject ties in well with your post and provides valuabale insight into the association between LA intake, endocannibinoid synthesis, food intake, food efficiency (weight gain per calorie) and obesity

http://www.ncbi.nlm.nih.gov/pubmed/?term=22334255

The study fed groups of mice 1% ALA with either 1% LA, 8% LA or 8% LA plus 1% EPA+DHA on medium fat diets (35% of calories) and high fat diets (60% of calories)

The classic method of inducing obesity in animals is by feeding a high fat diet (60% of calories) that includes 8% of calories as LA. It was found that mice fed the high fat diet (60%) with 1% LA and 1% ALA did not become obese and actually weighed less than mice on the on the medium fat diet with the same PUFA intake. A high fat diet therefor does no necessarily cause obesity. The dietary intake of 1% LA and 1% ALA is of course far from an average diet.

When mice were fed 8% LA the observed red blood cell (rbc) AA content as % of HUFA was about the same for both the medium and high fat diets and fairly consistent with rbc AA content calculated by the Land's equation. In the liver, however, AA content increased by 75% on the medium fat diet and 160% on the high fat diet and endocannibinoids increased proportionately. Increasing LA intake from 1% to 8% resulted in an increase of 25% the adiposity index of 25 % of mice on the medium fat diet and 42% in those on the high fat diet.

It is of interest that when LA intake was increased from 1 to 8% of calories, food intake did not increased on mice fed the medium fat diet but increased by 17% in mice on the high fat diet. However, food efficiency (weight gain per calorie) increased by 13% on the medium fat diet but only 3% on the high fat diet.

The increase in food efficiency resulting from high LA intake is the reason that LA contributes to fatty liver as you have noted in previous posts.

Jane said...

@Gretchen
'I gained weight without eating a lot of processed foods, unless you consider rice processed... I also ate homemade French bread... My problem was not junk food but simply too much food...'

Could I ask you please, was the rice white rice? And was the French bread white bread? There is evidence that the micronutrients removed from white flour and white rice can stop you from eating 'too much food'.

A paper published in 1976 by the eminent biochemist Roger Williams, discoverer of vitamin B5, showed that rats eating an American-style diet with refined carbs ate 60% more of the sucrose they were offered than rats on the same diet supplemented with micronutrients.
'Potentially useful criteria for judging nutritional adequacy'
http://ajcn.nutrition.org/content/29/7/710.long

realitybites125 said...

Stephan this approach couldn't be anymore true for me. I am a paleo dieter but have failed to lose weight in the past because I followed a more relaxed, even primal, style where I would allow myself to eat salt, dairy, etc etc. Basically tasty stuff.

In the last few weeks I decided to make that change again but when strictly paleo and in a sense I have cut all the reward foods out of my diet. I thought it was going to be very difficult, but in actual fact, I have adapted rapidly, don't miss the foods at all, don't feel as hungry, and the weight is moving off fast!!!

Have you ever considered how there are many parralels with what you propose and a more pure paleo approach, but how deviations on paleo are really to gain access to these more highly rewarding foods (ie bacon, dairy etc) that people enjoy thus undermining the results?

mark Rand said...

Gretchen you are correct. In the end energy balance rules period. The term highly palatable foods is subjective and the term junk food is vague at best.

Whatever one's perception of "highly palatable foods" is the result is the same. Foods that taste exceptionally well tend to be calorically dense. In other words less volume. Couple that with the fact it tastes good and a person ends up in constant positive energy balance day in and day out. Being habitual creatures, we don't like not having what we are used to having especially when it brings pleasure in the manner delicious food does. (We have confused treats and eats) Same can be said for alcohol, sex and even exercise when it becomes the norm for many.

I've joked for years how I would like to write the "Crappy Food" diet book! Simply pick foods you really don't enjoy and you'll lose weight, somehow I don't think that will sell??

The irony of that is, after a short two weeks the crappy food diet might backfire as what they didn't like becomes likable! Our taste buds are very adaptive. The good news would be most people when faced with picking foods they don't like as well would tend to pick foods that are less calorically dense per volume.

SamAbroad said...

Gretchen,

Were you grinding the wheat from scratch to make the bread or did you buy bleached flour? Because that is already processed and what I would consider a junk food. Definitely not as bad as potato chips or other snack food, but you can see problems accross populations upon the introduction of white flour in the early 20th century.

I know what you mean about high-end restaurant cuisine being more palatable. I will certainly enjoy it more than stale popcorn at the cinema, but I am far more likely to overeat the stale popcorn.

I think this is one area in which palatability and reward can oppose one another.

Travis Culp said...

If one overlooks the points made here, the acrylamide content, the rancid seed oils and so forth, the fact that they are made from potatoes does make them actually fairly nutritious.

I was surprised to see that the potassium content actually exceeds the sodium content in most potato chips.

That all being said, I don't eat the things, but it's something to keep in mind for Apocalypse Nutrition where your band of road warriors occasionally stumbles on a cache of infinitely-preserved junk food.

Jack C said...

Supplemental information regarding my previous post on potato chips, linoleic acid, endocannabinoids and obesity.

In a medium fat diet (35% of calories), increasing rodent dietary LA from 1% to 8% of calories resulted in a 25% increase in the obesity index due almost exclusively to increased food efficiency (weight gain per calorie of food intake) There was no increase in food intake.

In contrast, in the high fat diet (60% of calories) the same increase in LA resulted in a 42% increase in the adiposity index primarily due to increased food intake. There was very little increase in food efficiency. The resulting food efficiency in high fat mice was 15% less than that of mice fed medium fat diet.

The reason for the LA induced increase in weight gain per calories of food in the medium fat compared to the high fat diet is that endocannabinoids stimulate the liver to increase "de novo lipogensis", or conversion of carbohydrates to fat, and the medium fat diet contained more than twice the amount of carbohydrates contained in the high fat diet (45% vs 20%)

In the high fat diet, increasing LA intake resulted in a 165% increase in endocanaibinoids (twice that of the medium fat diet)and a 17% increase in food intake which caused a 42% increase in adiposity index. Other studies have shown that a high fat intake combined with high LA intake results in a greatly increased endocannabinoids and the development of a preference for high fat foods (An addiction to high fat foods)

When the rodents fed 8% LA were given 1% n-3 HUFA (EPA and DHA), red blood cell AA returned to the same level as mice fed 1% LA but the reduction in adiposity was only half of the previous increase.

Current average intake of LA is about 8% of calories compared to 2.2% in 1909. Most of the increase in LA intake is due to increased consumption of stuff like potato chips high in vegetable fats. Increased soy bean oil consumption accounts for most of the increase in LA intake.

Reducing LA intake to 1909 levels will only partially reduce the de novo lipogeneis of a medium fat diet and the addictive effect of a high fat diet UNLESS the AA content of red blood cells is reduced to about 42% by consuming about a half teaspoon of fish oil (by my calculation).

My dietary LA has probably been on the order of 2% of calories for many years (no potato chips) and my fat intake is probably about 60% of calories mainly due to my love of whole fat raw milk, cream, butter and cheese from pastured cows.

Increased fat synthesis by the liver not only increases adiposity but also increases risk of fatty liver. It is my reasoning that a person has no control over the increased lipogenesis that occurs on a medium fat diet but a person can, to some degree, control their food intake when on a high fat diet. So I will stick with the high fat diet and my daily dose of fish oil in order to stay lean.



In-Cybertown said...

Very interesting my understanding is that junk food is very addictive therefore over indulgence is inevitable in many cases, great blog thanks

Kona C said...

@ Jack C

If you revisit this post and read this, would you mind getting in touch with me? I would like to chat with you about the subject you posted.

pawortz@gmail.com

Dianna said...

No arguing over carbohydates, eat meat only, the only human diet