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Sometimes, I turn into a food zombie. Know the feeling? You don't want to eat, but you're a bit peckish, and something — often a powerful TV image of steaming, gleaming meat or pasta — sends you staggering, arms outstretched, to the fridge or the cupboard, to rummage until you find something to sate the craving.
It's such a deep urge that I wasn't a bit surprised to learn from Dr. Mark Andermann of Beth Israel Deaconess Medical Center that it emanates from "the bottom of the brain."
Andermann is co-senior author of a study just out in the journal Nature that helps pinpoint what happens in our brains when delicious images turn us into food zombies — except it talks about "homeostatic circuits" that "gate food cue responses," not zombies. It finds that by manipulating just a few thousand neurons, it's possible to make a mouse that's just eaten the equivalent of Thanksgiving dinner start noticing food cues and eating again. And the opposite as well: In a hungry mouse, you can tweak specific neurons to block the response to food.
"[T]he idea that it's willpower and you can shut it off at will -- it's much more complicated than that."Dr. Mark Andermann
"This shows that there are specific pathways that control how much someone is going to react to food," he says, "and so the idea that it's willpower and you can shut it off at will — it's much more complicated than that."
Our conversation, edited:
How would you sum up what you found?
MA: Every day, when we become hungry, our body tells us we need to find food. And people had found in many studies in humans that there are parts of the cortex, the outer bark of the brain, where hunger is driving you to find that food. But nobody understood the pathway from hunger to this craving. And we used special tools in mice to figure out the pathway from neurons involved in hunger to this brain region involved in cravings, or at least one part of it.
So, you've pinpointed the precise pathway by which hunger influences our reactions to pictures of food? How does that play out in our lives?
You know how, when you're driving down the highway, and you see a picture of a fast food joint, you start thinking about that cheeseburger and start salivating? But if you've just finished Thanksgiving dinner and you see that same sign, you're not going to think that cheeseburger is very appealing anymore.
So what exactly have you figured out about that?
What we figured out is that there are these neurons, just a few thousand neurons in the bottom of the mouse brain, and you can turn them on directly using new tools. And when you turn them on, even in a mouse that's eaten its equivalent of a Thanksgiving dinner, you can restore that mouse to a state where it's eating another 10-15 percent of its body weight in food, and where its brain looks for all the world like a hungry brain.
So what could this mean for obesity?
First, this shows specific pathways that control how much someone is going to react to food. And so the idea that it's willpower and you can shut it off at will, this pathway shows that it's much more complicated than that.
And we need to understand how the brain is telling us to look for food. It's told us to do this for millions of years, and it's only now, in the last 200 years, that that's become a bad thing. So we need to understand how the brain is forcing us to pay more attention to food than we want.
And then maybe we could block that?
I think that's the exciting thing about what we're doing: We are taking brain areas that have already been implicated in humans to go off the tracks in obesity, and also in restrained dieters, where you're trying to keep back from eating that delicious cupcake but you just can't get your eyes off of it. And what's been troubling is that there are millions of cells under the hood in any of these human imaging studies, so which ones are the ones that we need to go after? And which ones are the ones we can develop drugs to target?
Now we have a picture, at the level of individual cells, of which ones are the ones that are reacting to food. And we have tools that are coming out of amazing research in the last couple of years that let us look at the inner genetics, and the inner life of each cell, and try to figure out which cells have which receptors that we can then target with which drugs.
That's extremely exciting because it's like we're finally trying to fix a car when we now understand a little bit about how it works. We have a long way to go, but until recently we couldn't do much to fix it beyond giving it a new paint job.
So could this finding really lead someday to drugs that could help stop food-cue-related cravings?
I wholeheartedly believe that's the case. And the pathway that we found between the bottom of the brain and the top of the brain is the main reason we're excited about that. Because once you get to the cortex, you're in a part of the brain where it's probably being used for all kinds of things, like eating, drinking, riding a bike, feeling pain. But there might be places along the way from the hunger centers up to the cortex which can selectively tone down the attention to food and not really disturb attention to other things that are really healthy in your life.
So you got the brains of sated mice to react like hungry mice. But of course, for obesity what we really want to do is the opposite: Get hungry mice to have brain reactions like sated mice. Did you try that?
We did try that. We went in and we selectively disrupted that pathway in between, and we found that it made the animal stop reacting to these food cues. We were really excited about that, because you could shut off the insular cortex, which is the craving part of the pathway that we can now image, and the animals, if they had access to healthy food in their home cage, they'd eat it just like they did before. They'd even eat the same milkshake that we had been giving them. But if they had to react to these food pictures, they stopped doing that. So it's like finding a sharper scalpel or knife by which to separate out deliberate eating, for example during a meal, versus reacting to that food advertisement.
What's really cool about this is that these sated mice had all the usual hormone activity involved in feeling full, and yet turning on a few thousand neurons at the bottom of the brain — these specific neurons called AgRP neurons — basically short-circuits most of that. And that's, to me, one of the most surprising and exciting aspects of this.
And can this paper offer new insight into the virtually irresistible power of these cravings?
I think it offers insight in the sense that it kind of blew us away that you see this strong reaction in the cortex when you present a picture of food to a hungry mouse, but that when the mouse has finished eating as much as it wants, that reaction, throughout the entire brain region, is now practically silent when you present the same picture of food.
The magnitude of that effect, both in our mice and in the same brain region in humans, really speaks to the fact that entirely new, entirely different brain circuits are being turned on and recruited, and are exploding with activity, when you're in this hungry state versus when you're sated.
You know the diet advice that you need to not keep food you can crave around in your house? I guess that's because your insular cortex, the part of the brain you're focused on, can go so wild you can't fight it?
Exactly. Once the information gets sent to your insular cortex, the insular cortex is helping you make this decision: Is this going to make me feel good? But is this better than the aversive consequences?
And that's fine if you're some starving animal trying to decide if something has gone off or if it's worth eating. But if you're getting posed that question a thousand times a day with food commercials, and with delicious foods in your house, eventually the insular cortex is going to lose that battle, because it can only fend it off for so long. And that's exactly why, in my own house, I go home and I try to feed my kids as much fruit and vegetables as possible. That's a difficult battle, probably harder than what I do at work.
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