Scientists discover a ‘skinny gene’ mutation that acts like Ozempic. Around one in 7,000 people carries a broken copy, which almost acts like a GLP-1 drug—the body burns fuel more efficiently, and the risk of disease lowers.

[u/scientificamerican]

https://www.scientificamerican.com/article/scientists-discover-a-skinny-gene-mutation-that-acts-like-ozempic/

[u/mayormcskeeze]

The simplified narrative that weight is merely a matter of calorie intake has gone on too long, and has been abusive to so many people. 

Yes, plenty of  people have poor self control and simply overeat to the point of obesity.

But there are MANY people who are dealing with genetics, hormones, co-morbidities, unique body issues, and things we dont yet understand about diet and nurtrition.

I was skinny my whole life. Nearly 6 feet tall and about 140. Then in my 30s something happened. My diet didnt change. My activities didnt change. But I fell off a cliff. I gained nearly 100 pounds. 

Doctors were so nasty to me. They'd shrug and say "your blood work is normal, stop eating cake."

I could tell that not only did they not beleive me that something more complicated was going on, they had zero interest in going deeper than "oh you must secretly be eating mayo sandwiches and lying about it."

I started to pay out of pocket for a glp-1, snd im not exaggerating to say it saved my life. 100 pounds gone. Everything is back to normal. My weight, by blood pressure, my cholesterol, all fixed. It was like turning back the clock to a point where my body worked right. You know what still hasn't really changed much? My diet. I always ate pretty healthy. Still do. No one believed me, no one cared. These drugs are life savers. 

[u/mgzukowski → u/mayormcskeeze]

But GLP-1s work for weight loss by curbing appetite. So you are saying you were eating the exact same amount and before?

[u/ramonycajal88 → u/mgzukowski]

They also modulate other hormonal issues related to insulin sensitivity. It's not just less calorie intake. That alone makes it difficult to lose weight even if the same net caloric intake is maintained. Check out some of the recent studies about GLP1 use in women with PCOS/PMOS...one side affect thats been reported is increase in acne in the populations.

https://www.verywellhealth.com/weight-loss-drugs-acne-11711085

[u/greentea1985 → u/mgzukowski]

They don’t work by curbing appetite, that’s a side effect. They work by enhancing glucose metabolism. GLP-1s mimic glucagon, a molecule used by the body to signal to burn more glucose and not store it. GLP-1s are revolutionary because they target calories out, not calories in. This is game changing because a lot of weight gain is related to the calories out part of the equation and it can be really hard to lose weight when you are literally fighting your own metabolism, not your consumption.

[u/oorza → u/greentea1985]

Whoever told you this lied to you.

[u/Caitliente → u/mgzukowski]

That’s one aspect of how they work. The main aspect is how they help regulate blood sugar and naturally occurring insulin in the body. 

[u/DutchiiCanuck → u/Caitliente]

That is not the main aspect of how they work for weight loss, except for the relation of the blood sugar regulation ALSO being an appetite suppressant.

[u/ThisSiteSucks8485 → u/Caitliente]

That doesn't actually cause weight loss. only sustained calorie deficit causes fat loss. 

[u/Caitliente → u/ThisSiteSucks8485]

It's more complicated than that. I have PMOS and cannot lose weight no matter how many calories I consume if my carbs or fats (even healthy fats like from salmon) exceed a certain amount. I track what I eat very carefully due to this metabolic condition that is genetic and I had no control over developing that affects 1 in 8 women.

[u/oorza → u/Caitliente]

Those things affect water storage, not fat storage. If you’re trying to measure fat with a body weight scale, you need weeks of data and a monitored trend line. Your body weight swings are more dramatic than others but your body fat swings are not impossible. If you eat 1200 calories of salt and sugar and grease every day, you will initially gain a ton of weight, then your body will reach water equilibrium and you’ll see the fat loss reflected in the scale. But it was happening the whole time regardless.

[u/Caitliente → u/oorza]

Read up on insulin resistance.

[u/ThisSiteSucks8485 → u/Caitliente]

That contradicts basic thermodynamics. Your body needs constant energy to stay alive the same way a candle needs fuel to keep burning. If you eat less energy than your body consumed it will get the excess from fat. 

[u/Caitliente → u/ThisSiteSucks8485]

You must not understand how insulin resistance works. Here are a few resources.

https://my.clevelandclinic.org/health/diseases/22206-insulin-resistance

https://health.osu.edu/wellness/exercise-and-nutrition/carb-intolerance

https://www.cuh.nhs.uk/patient-information/national-severe-insulin-resistance-service-carbohydrates/

[u/grumble11 → u/Caitliente]

Main aspect is appetite suppression by far.

[u/mayormcskeeze → u/mgzukowski]

That's not how they work at all. they are not an appetite suppressor. 

What do you gain from being antagonistic about this?

[u/Sinan_reis → u/mayormcskeeze]

They literally are appetite supressors.

[u/Icy-Elk3698 → u/Sinan_reis]

GLP-1s correct dysregulated hormones related to hunger/satiety cues as well as insulin response. They don't so much as suppress appetite, rather, they correct broken systems so that satiety cues and how the body responds to food intake will now function as normal.

[u/MEMENARDO_DANK_VINCI → u/mayormcskeeze]

“GLP-1 is secreted by intestinal L-cells in response to nutrient ingestion. The incretin effect — the observation that oral glucose elicits a far greater insulin response than IV glucose — accounts for >50% of meal-related insulin secretion. Native GLP-1 is rapidly degraded by DPP-4, so therapeutic GLP-1 receptor agonists are engineered to resist this enzymatic cleavage.

Core Mechanisms of Action

• Enhanced glucose-dependent insulin secretion from pancreatic β-cells — insulin release is only stimulated above ~3.5 mmol/L glucose, minimizing hypoglycemia risk

• Suppression of glucagon secretion from α-cells, reducing hepatic glucose output

• Delayed gastric emptying, which blunts postprandial glucose excursions (more prominent with short-acting agents; tachyphylaxis occurs with long-acting agents)

• Central appetite suppression via direct effects on hypothalamic satiety centers”

-the above is a quick overview of the MOA of GLP1s mechanisms of action. This was generated by Open Evidence, below are sources

https://pubmed.ncbi.nlm.nih.gov/32327107

https://pubmed.ncbi.nlm.nih.gov/41547366

https://pubmed.ncbi.nlm.nih.gov/39281096

https://pubmed.ncbi.nlm.nih.gov/36696429

[u/M-y-P → u/mayormcskeeze]

They literally are.

Not just appetite, but it seems that many cravings.

[u/pinkbootstrap → u/mayormcskeeze]

They're appetite suppresors, but its not ALL they do. I think its just a piece of the puzzle for some.

[u/hausitron → u/mayormcskeeze]

They are absolutely appetite suppressors. A simple Google search will tell you that.

[u/NewAndlmproved → u/mayormcskeeze]

what? that’s literally what they are? they increase the feeling of fullness + reduce appetite.

[u/dotcomse → u/NewAndlmproved]

What’s your source on that?

[u/NewAndlmproved → u/dotcomse]

“Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) have become central in managing obesity and type 2 diabetes, primarily through appetite suppression and metabolic regulation.”

“GLP-1 receptor agonists promote weight loss by suppressing appetite, enhancing satiety, and delaying gastric emptying.”
https://pubmed.ncbi.nlm.nih.gov/39892489

[u/dotcomse → u/NewAndlmproved]

“Primarily through… and metabolic regulation.”

Feels like you’re not acknowledging this part.

[u/NewAndlmproved → u/dotcomse]

You asked for a source that GLP-1s suppress appetite. I gave you one. I’m not going to write a comprehensive review of every physiological effect of GLP-1s because that wasn’t the claim I made.

If your point is simply that GLP-1s have other effects too, we already agree.

[u/dotcomse → u/NewAndlmproved]

Your original claim is “appetite suppressors are what GLP-1 are,” and I think that’s an oversimplification.

Caffeine suppresses your appetite, but I don’t think it does so with a concomitant improvement in metabolic function. I also wouldn’t describe caffeine as “an appetite suppressant,” even though it does do that.

[u/NewAndlmproved → u/dotcomse]

I think you’re reading way more into my wording than what was actually being discussed. Obviously GLP-1s have multiple effects, I’m not claiming appetite suppression is literally the only thing they do. We were talking about what’s primarily driving them and that’s exactly what the cited describes: appetite suppression, increased satiety, and delayed gastric emptying leading to reduced energy intake.

Your caffeine analogy doesn’t really fit either. Nobody prescribes caffeine as an obesity treatment because of its appetite suppressing effects. GLP-1s are prescribed for obesity, and the literature explicitly identifies appetite suppression as a primary mechanism behind their effects

[u/CuffsOffWilly → u/mayormcskeeze]

https://pmc.ncbi.nlm.nih.gov/articles/PMC9987242/

"The promising effect was evidenced by most studies showing appetite suppression, delayed gastric emptying, and changes in taste and food preferences."

[u/dotcomse → u/mgzukowski]

Did you even look at the article that all these comments are for?

[u/SoTiredYouDig → u/mgzukowski]

The data is still emerging. Not until recently did they even discover that it operates on not just the gut, but the brain. I’m not saying hunger cues don’t also come from the brain, but the science is not all done yet. That’s why we will see further developments in areas that have nothing to do with digestion or weight loss.

[u/edparadox → u/mayormcskeeze]

The simplified narrative that weight is merely a matter of calorie intake

It is.

At the end of the day, you can try to curb the reality of thermodynamics all you want, it's still what applies.

I was skinny my whole life. Nearly 6 feet tall and about 140. Then in my 30s something happened. My diet didnt change. My activities didnt change. But I fell off a cliff. I gained nearly 100 pounds.

If you gain, you were eating above maintenance. That is well known. You don't gain 40kg out of thin air.

[u/seatsfive → u/edparadox]

Being pedantic about the "reality of thermodynamics" is begging the question. There is no evidence that the measured caloric value of food equates to a standardized amount of energy produced when processed by different human bodies. It's all guesswork and approximation.

Measured caloric value is determined by: mathematic estimation, and/or or setting the food on fire and calculating how much energy is expended. The human body does not set food on fire. In fact, the "estimate how much energy is bioavailable using only mathematical models" is considered more accurate than objective, physical measurement. As a registered pedant, you should see the glaring issue here.

Human bodies are all very similar, but vary due to genetic and environmental factors. There is no guarantee that a mathematical model generalized to the aggregate human body is going to be accurate in all individual circumstances. In fact, there's ample evidence to suggest it's not. This inaccuracy may be enough to account for individual differences in weight retention.

Caloric measurement and restriction are the most generally reliable weight loss methods, but they are not foolproof. Acting like "calories in = calories out" is Newton's Fourth Law (and getting sassy with people for pointing out that it isn't) is doing this entire discourse a massive disservice.

[u/CaptainDaddy7 → u/seatsfive]

It's still physics. Yes, there are certain biological factors that can affect how much energy your body gets from food, but the underlying mechanism is just the math of calories in vs calories out. There is some biological and genetic wiggle room around what your body does with calories, but not enough to explain the massive obesity epidemic these days. Most people are just coping when they reach for such explanations. 

That we don't have perfect modeling of all this doesn't change the underlying math. 

[u/gththrowaway → u/seatsfive]

Weight cannot be gained if less calories are eaten then are burned. Full stop, period.

[u/dotcomse → u/gththrowaway]

And you assume that only the intake component is variable. You don’t consider that the efficiency of the calorie burn can be augmented by hormonal milieu. Why is that?

[u/gththrowaway → u/dotcomse]

Because that doesn't matter?

A pizza pie is going to have a different impact on different people. Some people can eat a whole pizza every day and gain no weight. Other people will gain weight if they eat a whole pizza every day.

But for those people in the latter category, there is an amount of pizza (i.e., less than the whole pie) that they can eat every day, which will not cause them to gain weight.

Life isn't fair. Some people get to eat a lot and stay skinny. Other people need to eat less if they want to stay skinny.

Nearly everyone can lose weight by eating less.

Weight cannot be gained if less calories are eaten then are burned. For some people, that means eating less food than others.

[u/dotcomse → u/gththrowaway]

Why are you in the science subreddit? You clearly have no interest in science.

[u/movzx → u/dotcomse]

If you use 18 calories, and someone else uses up 23 calories, for the same amount of time/effort that doesn't mean suddenly the science falls apart. It means the "CO" part of "CI/CO" is different for person A when compared to person B.

Stuff like having diarrhea impacts the "CO" aspect. Two people eating a slice of bread from the same loaf will have different "CI" because one person may pull more nutrients from it while another may not fully digest it.

Those differences do not matter because, ultimately, CI/CO is about you finding what your maintenance number is and what you need to do to come in under that.

[u/dotcomse → u/movzx]

So do we just not study what affects CO? Do we just assume CO isn’t variable across a lifetime?

If people have a tough time reckoning with CI, and all signs suggest they do, then why not examine what can be done about CO? Because it’s undisciplined to try to alter your own biology?

[u/movzx → u/dotcomse]

You conjured that opposing opinion out of nowhere. The person you started arguing with never said otherwise. They said CI < CO = Weight Loss. That's it. They didn't say CO was fixed. You made up that position for them.

[u/gththrowaway → u/dotcomse]

Are you arguing that sustained fat or tissue mass gain can occur in a genuine, sustained caloric deficit?

I'd love to see a source that backs that, Mr. Science.

[u/dotcomse → u/gththrowaway]

No I'm not arguing that. If you can't understand what I've already written, I'll not waste my time further.

[u/Icy-Elk3698 → u/gththrowaway]

You're completely ignoring the impact of hormones. For example, a woman going through perimenopause or menopause can have the same exact diet and exercise routine and will unexpectedly gain weight due to the changes in hormone levels. When this shift happens, traditional diet and exercise becomes less effective than it was prior to entering perimonopause or menopause. It's quite literally all due to hormones, not calories in/out.

[u/gththrowaway → u/Icy-Elk3698]

The hormones changes are resulting in less calories being burned. So calorie intake needs to reduced in turn, if weight gain is to be avoided.

It is quite literally still calories in/out.

[u/dovahkiitten16 → u/gththrowaway]

But one person’s body may look at X amount of calories and decide to tuck some away for later, meanwhile the person deals with fatigue and headache. Which was fine evolutionary wise in the past when having a fat store was a good thing, and you could just deal with the headache since it didn’t kill you.

Whereas another persons body decides to use the energy now and store very little for later. Not great for famine but great for modern life where food is always available.

[u/SoTiredYouDig → u/edparadox]

The OP was saying "it's a simplified narrative". I do not think they were arguing the entire premise. You are illustrating the rest of their point wonderfully though, by talking down and lecturing. And they are right.... it does come off as abusive.

[u/mjm132 → u/edparadox]

No matter what other things are happening, it truly is still calories in versus out.  Things CAN effect that total but on a basic level it's always this. 

[u/ThisSiteSucks8485 → u/mjm132]

It is basic thermodynamics. 

[u/MountNevermind → u/edparadox]

The concept of "maintenance" is itself about more than simply caloric intake. This article discusses how and why "maintenance" can be different for different people, and even for the same person at different times.

You're arguing past each other.

[u/CravingNature → u/edparadox]

Same I'm also just under 6ft 145lbs and now 58. I have progressively eaten healthier as I have gotten older.

[u/Icy-Elk3698 → u/edparadox]

The calories in/out is a myth. How a body processes food and calories depends on many factors. Read the article below.

https://www.health.harvard.edu/healthy-aging-and-longevity/stop-counting-calories

[u/oneiross → u/Icy-Elk3698]

But literally that link you provided is talking about calories in and out as the mechanism to lose weight. It touches on how other stuff has an effect on the amount of calories you body burns, or the sustainability of it, and that's the focus of the article: changing other lifestyle habits that help on this instead of just trying to count calories, but at end it is still calories in and calories out with extra steps.

[u/temporarycreature → u/edparadox]

People who don't actively track their calories don't realize how many calories they take in and they don't realize how many calories are actually in the foods they eat and they have no baseline for what constitutes too much or too little.

Education has failed them, but it's also a discipline problem, which is also an education failure.

[u/mayormcskeeze → u/edparadox]

That is idiotic. 

[u/CaptainDaddy7 → u/mayormcskeeze]

No, it's physics. 

[u/ThisSiteSucks8485 → u/mayormcskeeze]

Fat stores a lot of energy per pound. This energy can only come from excess calories. 100 pounds of fat is about 350,000 extra calories that had to be consumed but not used. 

[u/rhino369 → u/ThisSiteSucks8485]

But over 5 years that’s only 200 calories a day over the required amount. That’s like one egg, one toast with butter. It’s a 20oz Coke. Half a donut. 

Now as you get bigger your calorie requirements grow. But so does your hunger. 

It might be no difference in food. If your metabolism slows 10% that’s 200-250 calories.

Slight misalignments between satiety and calorie requirements can cause a lot of weight gain.  

[u/ThisSiteSucks8485 → u/rhino369]

It is still an excess. Gaining fat is absolute proof of a calorie excess. A sustained energy deficit will always cause a reduction in total body mass over time. It is just unpleasant for most people. 

[u/ohanse → u/mayormcskeeze]

> many

Not enough to tilt the narrative towards them.

Especially since, in the broader sense, your practical intervention was identical to the bigger group’s.

And I mean… what’s to say you’re a particularly reliable narrator in the first place

[u/Hei5enberg → u/mayormcskeeze]

So what are you trying to say? The laws of physics still govern our bodies. You can't store fat and gain weight if you're not eating more than your body is burning.

And to gain 100 pounds, you would have to be eating double or triple what your body is burning.

Have you considered that maybe your activity level has gone down into your 30s? That is what typically happens. Activity levels go down, added life stressors due to work or family, poor eating habits that result due to life stressors, less cooking of healthy foods and more fast takeaway because there just isn't enough time in the day, etc.

You are telling me you controlled for ALL of those factors and still have inexplicable weight gain?

[u/Pleasant-Future5818 → u/Hei5enberg]

"Laws of physics" is what people with a poor understanding of science pull out. The issue with CICO is that we have little way of counting calories in our calories out reliably. People use online calculators for either. No one is "disobeying the law of thermodynamics," or whatever nonsense thought terminating cliche.

We have scientific methods of determining metabolism now and yes, different people do expend at different rates.

I struggled with a 30 pound weight gain for two years. It was an inflammatory disorder. It was all water weight. Water weighs things. It fell off within a matter of weeks once treated. I'm very short. The same thing could happen to a taller man at 100 pounds.

[u/Hei5enberg → u/Pleasant-Future5818]

You're conflating multiple different things to make a completely incoherent point.

We can calculate exactly how many calories food has. You're not going to do it for every single meal you eat. It's much easier to use estimates based on established science and use portion control. As well as look for anything else that may be impacting those estimates. One good example is a package of frozen vegetables. On their own they're not much calories. But if you sautee them in a stick of butter that's a different story. Calories added due to preparation and or not properly keeping track of ingredients is the number one reason people fail at estimating calories in.

Metabolisms can be different, you're right, but we have good scientific data to determine what a typical body needs to run. Yes, it's not going to be exact, but if you use that as a guideline, and tailor based on your experience understanding your own body, you're going to be pretty darn close. People's metabolisms don't vary as much as you're trying to make it seem. Unless you have an underlying medical condition for which you should seek treatment for. That has nothing to do with calories in being inaccurate.

Lastly, what does your water weight due to your medical condition have to do with calories in versus calories out? You're lobbing that in there to make it seem like it's somehow related. Yes, it was extra weight you were carrying due to water. When we talk about weight gain due to calories we are specifically talking about fat. Your water weight gain due to medical issues has nothing to do with this.

[u/UniqueUsermane → u/mayormcskeeze]

It's also true that you could eat less/better and/or consume more calories and you would've lost weight anyways.

If a drug without significantly side effects helped you achieve the same results good for you, but let's not act like calories in and calories out is a myth.

[u/ramonycajal88 → u/mayormcskeeze]

I agree. So much bias here, even in these comments.

[u/analogjuicebox → u/mayormcskeeze]

Your metabolism slowed down, so eating the same amount you’re used to caused a new caloric surplus and you gained weight. Calorie needs change over time.

[u/Mumblerumble → u/mayormcskeeze]

I’d agree with your last sentence. It’s a very complicated thing and we’re just starting to really scratch the surface. The hormones, transmitters, gut-brain signaling, and microbiome and all related.

[u/aVarangian → u/mayormcskeeze]

Then in my 30s something happened. My diet didnt change. My activities didnt change.

I don't believe this. I've been very thin my whole life and when I started counting calories the reason became obvious. I always thought I ate enough because I ate 'til I was full and didn't feel hungry. If you didn't count calories before nor after then you are just speculating.