this post was submitted on 04 Sep 2023
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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.

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[–] [email protected] 66 points 1 year ago (1 children)

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.

[–] [email protected] 29 points 1 year ago* (last edited 1 year ago) (1 children)

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.

[–] [email protected] 18 points 1 year ago (1 children)

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

[–] [email protected] 9 points 1 year ago* (last edited 1 year ago) (1 children)

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

https://edition.cnn.com/style/article/ancient-roman-feasting-history/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.

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[–] [email protected] 35 points 1 year ago (2 children)

Here’s todays winner for most unintelligible title

[–] [email protected] 22 points 1 year ago* (last edited 1 year ago) (1 children)

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...

[–] [email protected] 8 points 1 year ago (1 children)

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

[–] [email protected] 4 points 1 year ago* (last edited 1 year ago) (1 children)

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

http://achemicalhunger.com

[–] [email protected] 5 points 1 year ago (1 children)

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.

[–] [email protected] 4 points 1 year ago (1 children)

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

[–] [email protected] 4 points 1 year ago (1 children)

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.

[–] [email protected] 3 points 1 year ago (2 children)

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.

[–] [email protected] 3 points 1 year ago (5 children)

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.

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[–] [email protected] 6 points 1 year ago

I wanted a huge brain and am now thoroughly disappointed 😞

[–] [email protected] 33 points 1 year ago (2 children)

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.

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[–] [email protected] 23 points 1 year ago (3 children)

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

[–] [email protected] 18 points 1 year ago (2 children)

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.

[–] [email protected] 3 points 1 year ago

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.

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[–] [email protected] 14 points 1 year ago (2 children)

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.

[–] [email protected] 15 points 1 year ago (1 children)

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

[–] [email protected] 6 points 1 year ago* (last edited 1 year ago) (1 children)

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.

[–] [email protected] 5 points 1 year ago

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

[–] [email protected] 8 points 1 year ago (1 children)

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.

[–] [email protected] 9 points 1 year ago

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).

[–] [email protected] 4 points 1 year ago

Salt doesn't make you put on weight.

It's also all carbs, fat and protein.

[–] [email protected] 20 points 1 year ago (8 children)

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

[–] [email protected] 43 points 1 year ago (1 children)

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.

[–] [email protected] 7 points 1 year ago

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)

[–] [email protected] 42 points 1 year ago (3 children)

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.

[–] [email protected] 12 points 1 year ago

"almost nothing"? That's dramatic, and wrong.

[–] [email protected] 5 points 1 year ago (2 children)

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.

[–] [email protected] 20 points 1 year ago (1 children)

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.

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[–] [email protected] 19 points 1 year ago (1 children)

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.

[–] [email protected] 5 points 1 year ago

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

[–] [email protected] 4 points 1 year ago

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?

[–] [email protected] 24 points 1 year ago (1 children)

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...

[–] [email protected] 6 points 1 year ago (1 children)
[–] [email protected] 4 points 1 year ago

This hasn't worked for me.

[–] [email protected] 12 points 1 year ago* (last edited 1 year ago)

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.

[–] [email protected] 11 points 1 year ago (3 children)

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.

[–] [email protected] 9 points 1 year ago (3 children)

Nothing that could go wrong with raising body temp permanently...

[–] [email protected] 6 points 1 year ago

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

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[–] [email protected] 3 points 1 year ago

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".

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[–] [email protected] 7 points 1 year ago

But where does all the excess energy go?

Down the toilet

[–] [email protected] 5 points 1 year ago

https://slimemoldtimemold.com/2021/07/11/a-chemical-hunger-part-ii-current-theories-of-obesity-are-inadequate/ 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.

[–] [email protected] 4 points 1 year ago

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)

[–] [email protected] 17 points 1 year ago (1 children)

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

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[–] [email protected] 13 points 1 year ago

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

[–] [email protected] 6 points 1 year ago* (last edited 1 year ago)

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.

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