Brain's Weight Switch Found: May Let Us Eat What We Want, Finally

A new discovery reveals that astrocytes, star-shaped cells in the brain, play a key role in regulating fat metabolism and obesity. These cells act on a cluster of neurons, known as the GABRA5 cluster, effectively acting as a “switch” for weight regulation.

The MAO-B enzyme in these astrocytes was identified as a target for obesity treatment, influencing GABA secretion and thus weight regulation.

KDS2010, a selective and reversible MAO-B inhibitor, successfully led to weight loss in obese mice without impacting their food intake, even while consuming a high-fat diet, and is now in Phase 1 clinical trials.

tiny_electron,

But where does all the excess energy go? You can’t cheat basic physics

ParsnipWitch,

The digestive process is much more complicated than basic physics. There are all kinds of processes happening, some of them not yet understood, that regulate your appetite, weight gain, energy, etc. It’s different in each individual and for each individual it can change through various external factors.

geissi,

But where does all the excess energy go?

Down the toilet

Umbrias,

You just don’t digest as much nor store as much calories. So your feces and urine, as well as exhalation.

It’s not cheating basic physics, there’s just a lot of misunderstanding about how weight works in biology. Cico is not what many people believe it to be.

Natanael,

Absorbed calories in spent calories out would be more accurate, but nobody wants to do the more complicated math.

And some processes can technically be calorie neutral and still affect weight (like say how much water we hold)

jeremy,

I’m guessing the switch they’re discussing affects the tendency of the body to store excess energy instead of just passing it thru. That is: if you don’t pack it on, you push it out. If you know what I mean…

jcarax,

Time to invest in coffee.

cubedsteaks,

This hasn’t worked for me.

TheChurn,

Believe it or not, what you swallow has almost nothing to do with your weight. The only place the body absorbs energy from food is in the intestines, and the brain controls that process.

The digestive tract is a tube, open at both ends, through which food passes. The process of extracting energy from that food is complex and highly tunable: the brain controls the production and secretion of hundreds of enzymes and other chemicals, as well as the physical action of the muscles lining the tube.

The 'basic physics' here begins at the intestinal wall, not the mouth.

Hardeehar,

I mean technically, if it’s a tube, the mouth is part of the basic physics brain process. As in, if you don’t eat it, it won’t be added to the calories. The decision to eat is a brain process, too.

We’ve got drugs that play with that decision.

jhulten,

It’s also easy easier to discriminate against far people if you can define it as a moral failure of just not putting food in your gob.

Scribbd,

Unlike close people. Those are always bastards invading personal spaces.

jarfil,

Unless you don’t eat at all, the decision to eat is secondary to the decision to absorb energy from it.

For example, I’ve been eating a “healthy diet” with about the same amount of exercise, for the last 3 years: first it kept my weight steady, then I lost 70 pounds in 3 months, then gained 10.

The only difference: stress levels.

People have been congratulating me for losing weight getting stressed out of my mind to the point of almost going crazy and killing myself. Thanks, but I was better before.

StringTheory, (edited )

I hope you are doing better now.

Steeve,

“almost nothing”? That’s dramatic, and wrong.

forestG,

Believe it or not, what you swallow has almost nothing to do with your weight. The only place the body absorbs energy from food is in the intestines, and the brain controls that process.

I would believe it if I started gaining weight by just breathing. Also, no. Not the only place. Part of the alcohol consumed is absorbed through the stomach.

The digestive tract is a tube, open at both ends, through which food passes. The process of extracting energy from that food is complex and highly tunable: the brain controls the production and secretion of hundreds of enzymes and other chemicals, as well as the physical action of the muscles lining the tube.

The brain controls pretty much everything, and this everything is highly tunable. I mean, how else would well adjusted people adapt to the highly complex lives they live as adults? With commercial pills?

Natanael,

Look up nutrient bioavailability, which can vary between individuals.

The body can choose to absorb more or less (and the brain have no conscious control) by regulating absorption differently. This regulation is typically used to keep your levels of nutrients steady (some stuff we eat would be deadly in the doses we eat them if it weren’t for the fact that the body can simply dump most of the particular substance until we’re running low)

Emma_Gold_Man,

Since nobody else who answered you read the article:

Heat. They discovered a way to trigger the part of the brain that regulates heat production by brown fat tissue.

tiny_electron,

Thanks you! That makes a lot of sense

tryptaminev,

Nothing that could go wrong with raising body temp permanently…

curiosityLynx,

Just in! Man takes too many weightloss pills, ends up inadvertently cooking his testes! Read all about it in Blabbity Fair!

averagedrunk,

That’s kind of what DNP does. Side effects include death

LogarithmicCamel,

And in a world that is getting hotter and hotter, nothing is more appealing than carrying your own furnace with you, wherever you go.

CanadaPlus,

That’s the bit they mentioned, anyway. It sounds like in this scenario they tried two different diets, and the higher-calorie one produced more body heating. I imagine appetite regulation would also play a part “in the wild”.

meteorswarm,

slimemoldtimemold.com/…/a-chemical-hunger-part-ii… is a good analysis of why calories in calories out is both true and not a good model for how weight gain/loss works in people.

RobotToaster,

KDS2010, a selective and reversible MAO-B inhibitor

This seems like a really odd result. We already have MAOI drugs, they were the first class of antidepressant drugs invented accidentally in the 50s when they found the tuberculosis drug iproniazid made people happier. The selective and reversible MAO-B inhibitor selegiline has been used for years to treat parkinson’s disease. None of these drugs are known to induce weight loss.

naqahdah,

Every time I see one of these weight loss miracles, I wait for the other shoe to drop… and it usually does.

As I have learned the hard way in my own life, the weight loss miracle is setting a calorie limit and strictly adhering to it (barring medical complications… which, let’s face it, most of the people who say those cause issues with them losing weight probably don’t have them).

The weight loss miracle I’m waiting on is the pill that rewires your brain to change your relationship with food because, man… that’s the hard part. Having to constantly fight my own brain - no, you aren’t hungry, you’re bored; yes, you actually are satisfied eating a happy meal for 550 cals, you actually do not need a 2 cheeseburger meal large size at 1200 cals, and so on - that’s the struggle for me. I’m down from 270 to 240 so far, but I’d be lying if I said it wasn’t still a constant fight, which is probably what makes relapsing after taking all these drugs such a common thing.

beefcat,
@beefcat@beehaw.org avatar

The weight loss miracle I’m waiting on is the pill that rewires your brain to change your relationship with food because, man…

This is what the new class of weight loss drugs like Ozempic and Wegovy do. They also appear to help curb other addictions like alcohol. But good luck affording them right now.

naqahdah,

I had actually looked into that and yeah, because it isn’t technically indicated for weight loss most insurance companies have dropped covering it barring severe medical need. Unfortunately, I’m like 80lbs overweight, and even having high blood pressure wasn’t enough to drop the $300/no it would cost out of pocket.

It makes sense, I mean why cover $300/mo while I lose weight when you can cover my eventual six figure bypass and hospital stay, or roll the dice and hope I just die?

I did hear that there is some version of it that has (or is soon getting) approval for weight loss so… maybe!

CanadaPlus,

Well, that would be world-changing!

shiveyarbles,

Yeah I’m gonna nope on that. Messing with brain switchea so you can binge on food seems like an episode of black mirror.

CanadaPlus,

I imagine the way this would work it you’d just get full really quickly if you were eating something heavy.

PelicanPersuader,
@PelicanPersuader@beehaw.org avatar

ITT: People with extremely strong emotions about weight and extremely weak evidence to back up those feelings.

Raisin8659,
@Raisin8659@monyet.cc avatar

You can eat anything you like, as much as you like, followed by a pill. Sound like an environmental and social and poverty-problem disaster. Pretty much a theme of the Hunger Games.

jarfil,

The Romans called it “eat what you want, go vomit, keep eating”, nowadays we call that bulimia, coming soon: “eat what you want, take a pill, keep eating”… somehow makes me think that might not be healthy either.

Thorny_Thicket,

That’s actually a myth.

Macrobius uses the plural vomitoria to refer to the passages through which spectators could “spew forth” into their seats at public entertainment venues. Vomitorium/vomitoria are still used today by archaeologists as architectural terms.

Source

jarfil, (edited )

It’s not about Macrobius and the misinterpretation of Vomitoria, but about how Romans threw lavish banquets as a status symbol:

edition.cnn.com/style/article/…/index.html

Men eating reclined, for many hours on end, doing their necessities right at the table, getting served by slaves and women, throwing rests of food on the floor, purging (vomiting) between courses just to continue eating, with women kneeling or sitting beside them.

And then there were Bacchanalia, but those were more about drinking and sex… so not that far from modern uncontrolled parties, only now we have better drugs.

Obi,
@Obi@sopuli.xyz avatar

Yep, the Romans really knew how to party.

Centillionaire,

Or how about regulate the sugar and salt content in foods? No? More magic diet medications. Got it.

EquipLordBritish,

Given that it may be more likely for us to put up a Solar Shield than curb our fossil fuel usage, I think we are too stuck in a “fix things after the fact” culture than using preventative solutions.

xePBMg9,

The idea is to enjoy yourself without consequences.

millie,

I feel like their argument against it probably needs a little unpacking.

It seems a little disingenuous to me to only examine a model where carbon emissions don’t decrease and then attribute the result to the shield. If the shield is used in addition to reducing our carbon output we’d presumably be cooling things off in both the short and long term.

The result of failing to reduce our carbon emissions is already projected to be essentially apocalyptic in scope. The rest of the planet might luck out if our own actions reduce us to a population that we’re physically incapable of continuing to output enough carbon to keep warming it, but human civilization certainly doesn’t seem like it can survive keeping it up at the very least.

If we do get it together push against the wishes of the greediest humans and act as responsible stewards of the planet, it would be smart to try to save as much as possible. If a solar shield can help protect our biodiversity and the stability of our civilization while we get our collective shit together, that’s fantastic. It may even bring with it a sense of urgency and collective responsibility to fix the problem before anything happens to our buffer.

I get the arguments about the rapidity of change if the shield fails and the difficulty of animals migrating much more quickly, but if something doesn’t give soon they’re not going to have much of anywhere to migrate anyway.

At what point does the potential benefit of the shield outweigh the risk?

If I’m falling out of an airplane and my chute is kinda lopsided or whatever in a way that might strangle me if i don’t get my head out of the way, am I just going to let myself hit the ground instead? Or am I going to take the shot I’ve got and make the most of it?

We’re in freefall and the ground is down there somewhere, rapidly coming up to make friends. We need something now.

If this is it I say we take it. And we let it be the act that prompts us to be responsible with our planet.

Lmaydev,

Salt doesn’t make you put on weight.

It’s also all carbs, fat and protein.

storksforlegs,
@storksforlegs@beehaw.org avatar

The problem with regulating unhealthy food is that it is likely to jack up the price of the only affordable option for a lot of people. Maybe something like subsidizing and lowering cost of healthier foods to make them more affordable instead would be good.

deo,

There’s also a time component. Food can be quick, cheap, or healthy: but you can only choose two (at most). If people have to work for too many hours for shit pay, “unhealthy” becomes an undeniable option.

Sodis,

But that is only because of the current market landscape. Healthy food can also be packaged microwave ready and still be cheap. Most of the companies doing that just market it as healthy and charge a higher price for it (because people will still pay it).

BarrelAgedBoredom,

We dispose of 30-40% of the global food supply every year simply because it’s not profitable to sell it. It isn’t a supply issue. Subsidies are unnecessary. We could easily live in a post scarcity world if we could discard the profit motive

storksforlegs, (edited )
@storksforlegs@beehaw.org avatar

Oh I agree! I wish we could move past the profit motive as well, especially when it comes to food and shelter. Criminal that there are no non-profit options in these areas in most western nations.)

I was just arguing there have been campaigns to raise the price of sugary or convenience foods to get people to eat healthy. But these campaigns just end up hurting low income people who can’t afford the healthier options in the first place. I was suggesting an approach that might make healthy food more accessible - (but that’s within a shitty capitalist system.

BarrelAgedBoredom,

True that! A lot of legislation passed (if you’re in a country that actually believes in passing legislation) is often incomplete. Even within a capitalist system there can be some degree of a solution achieved. Austerity has thrown a wrench in that but we’ve seen that with enough pressure the state can occasionally help.

Perhaps (I’m in the US so my ideas may not apply elsewhere) instead of additional subsidies to agriculture we could reallocate the ones were already giving out to more nutritious crops. Corn gets far too much money for example, that’s why it’s in literally everything here. It’s so cheap it’s more cost effective to process the hell out of it and turn it into something else entirely over just growing something else. Likewise, dairy gets a ton of money and we waste so much of it.

That money could be given to a broader variety of crops, alongside some sort of legislation to make the disposal of perfectly good food either outright illegal or with heavy fines involved to the point that it’s more profitable/less costly to just sell the food. Hell, tax breaks for giving it away too. Because if there’s one thing that will get rich dicks on board it’s tax breaks. Maybe throw some additional incentive to move away from pesticides and monoculture as well

mookulator,

Here’s todays winner for most unintelligible title

Lmaydev,

I wanted a huge brain and am now thoroughly disappointed 😞

wahming,

Funnily, I understood that. There’s been a theory that our current obesity epidemic is caused by an environmental factor influencing our brains into targeting a higher ideal weight than it otherwise should. This is the ‘switch’ the title is referring to, and they’ve presumably discovered its existence and a way to influence it. Of course, there might be more than one…

Sodis,

The “switch” is most likely highly processed food and added sugar in everything you buy.

wahming,

There is good reason to think otherwise. You might find this an interesting read:

achemicalhunger.com

Sodis,

I do not have time right now to read the whole thing, but what strikes me as odd, is that the author blames everything on contaminants, when a change in lifestyle could also be an option. They write about indigenous people moving to western societies and becoming fat, blaming it on industrial food contaminants, but ignore, that western people do not exercise enough. At least mention it and give a reason why you think, that this does not factor into it.

Then they also generalize about people in the western world getting obese at the same rate, which is not true at all. People in the US are more obese than in the Netherlands, for example. Japan has one of the lowest average BMIs in the world. It just doesn’t add up. Furthermore, there is a lot of talking about causation, when they only prove correlation.

wahming,

All those factors are addressed at some point. Keep reading!

Sodis,

Nah, sorry, I was out, when they stated, that more exercise and eating less does not help (and then using an arbitrary time span of 12 months). If you violate the laws of physics in your analysis, it is definitely wrong.

wahming,

Calories in calories out is a pretty discredited theory, if that’s what you are referring to. The human body is not a closed system, so laws of physics is about as irrelevant as possible. The body can influence how much energy to absorb and burn, within limits.

Seriously, all the points you’re bringing up were fully addressed at some point in the article. It’s fine if you can’t be bothered to read, but it makes no sense to belittle it in that case.

Sodis,

The body can influence how much energy to absorb and burn, within limits.

Yes and with that you have an upper limit of how much energy food can give to your body. If your body does take less than this energy, you will lose weight even faster. It can’t take more energy than is provided by the food. Raise your exercise level above your maximum intake and you will lose weight. It’s thermodynamics.

wahming,

Seriously, all the points you’re bringing up were fully addressed at some point in the article. It’s fine if you can’t be bothered to read, but it makes no sense to belittle it in that case.

tryptaminev,

sorry, but i have to agree with @Sodis here. Calories in Calories out provides hard physical limits. If your article does nit acknowledge such fundamentals, it is questionable how reliable it is otherwise.

wahming,

It does. It’s amazing how many people will debate without reading the material under discussion. What do you want me to do, paste the whole thing in a comment? It’s the length of a short book. I would love to discuss it, but not if nobody else has bothered reading it.

Sodis,

I am trying, but it is just not well backed by data. The author goes on about diets all the time, grossly generalizing and totally ignoring, that it is also important how much you consume. They cite an example of France in the 1800s and say, that they ate more bread and butter (the link to the source not working). Okay, sure. And then they say, that they could still maintain their health easily, followed by the statement, that they exercised more, but this minor difference is not enough to explain it. Like, what are they going on about? In 1800 about two thirds of the population were working on farms, that’s not just “a bit more exercise”. And no word about food scarcity. People just couldn’t afford gluttony. Often enough they were just one bad harvest away from a famine. It’s ridiculous to assume, that they got to the same calorie intake on their bread, butter and dairy diet, that we have today with the amounts of sugar we eat and the affordability of food.

And while they probably exercised more on average than we do, the minor difference in exercise isn’t enough to explain the enormous difference in weight.

That statement is just plain wrong. Let’s say a minor difference in exercise is 50kcal a day. That’s about 6min running at 10km/h. This adds up to 18250kcal a year, which translates to over 2kg of body weight in ONE year. Multiply that by multiple years and it adds up quite fast. Keep that in mind for the following statement:

Many of them were farmers or laborers, of course, but plenty of people in 1900 had cushy desk jobs, and those people weren’t obese either.

Well, how did people get to these cushy desk jobs? By not available cars? How did they get their groceries? How did they clean their clothes? That’s all stuff, that takes a minimum of exercise nowadays. What did they do on their free time? It probably wasn’t sitting in front of the screen with minimal movement.

That’s just the first of these “mysteries” and the whole thing is written in this style. They take an observation and then give an explanation for it, that fits their narrative. Alternative explanations are either not acknowledged or ruled out on flimsy evidence.

Here, from the CICO part:

Sources have a surprisingly hard time agreeing on just how much more we eat than our grandparents did, but all of them agree that it’s not much. Pew says calorie intake in the US increased from 2,025 calories per day in 1970 to about 2,481 calories per day in 2010. The USDA Economic Research Service estimates that calorie intake in the US increased from 2,016 calories per day in 1970 to about 2,390 calories per day in 2014. Neither of these are jaw-dropping increases.

How are these not giant increases in calorie intake? This metric is per DAY. It adds up fast over years. We are speaking about 16kg worth of body weight in calories per year. Okay, they addressed this in the interlude:

Studies show that people with obesity eat and expend more calories than lean people. From this study, for example, consider this sentence: “TDEE was 2404±95 kcal per day in lean and 3244±48 kcal per day in Class III obese individuals.” From this perspective, the average daily consumption per Pew being 2,481 calories per day doesn’t seem like much — that’s about what lean people expend daily.

TDEE includes exercise. Class 3 obese is a BMI of 40, so for a 1.8m tall male, that is 130kg, lean is probably at the lower end of normal, so 65kg. Then you can calculate the basal metabolic rate for both cases, leading to 1655kcal/day for the lean and 2300kcal/day for the obese. The difference is exercise. So lean people burn ~800kcal worth of exercise while obese people burn ~900kcal, but at double the weight. Since calorie burning during exercise goes linear with weight, you can conclude, that lean people workout more than obese people. So their argument does not work.

I never said, that it would be easy to lose weight. It definitely is hard. Your body is adapted to your lifestyle and breaking out of your habits and completely changing your lifestyle can be extremely hard. However, blaming some mysterious contaminant will not help people lose weight. Especially, when things like liquid calories tend to add a lot to your calorie intake, but your body does not really register them. Our body has evolved to control its body weight over thousands of years to a different type of diet. I do really not know, why the authors think, that subjecting it to the modern day achievements of high calorie foods and liquid calories will not affect this balance.

wahming,

Thanks! This is exactly what I was hoping for, some critical analysis of the article’s methodology and conclusions. I’m not debating any of your claims above, just gonna use them as a jumping off point for more reading.

LogarithmicCamel,

This is not true. The laws of thermodynamics apply to open systems as well as long as you take into account the energy that enters and leaves the system, which is exactly what calories in, calories out mean. The brain influencing how many calories are spent is just part of calories out. What doesn’t work is equating calories out with imprecise estimates from websites, watches etc, or equating calories in with imprecise calorie counts from food labels that people often miscount anyway. But when calories are carefully measured by scientists (i.e. in a metabolic chamber) and everything is accounted for, it’s calories in, calories out all the way.

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