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Comment by AnthonBerg | Hacker News Reader

It's interesting with GLP-1 agonists that they all curb inflammation and redox stress.

–All of heart failure, addiction, and aging certainly have inflammation and redox stress as substrate.

It's interesting that GLP-1 agonists all have pulmonary effects. There's GLP-1 receptors in the lung.

(the lung is somewhat relevant in redox stress / burden / balance

as well as neuroendocrine metabolism. the lung is a metabolic organ. it metabolizes serotonin. serotonin has… many roles, anciently repurposed for a ton of things.)

It's usually the case that anything that, say, curbs addiction? will curb inflammation and redox stress, and have pulmonary effects. Exercise, for one. Psychological safety. Healthier eating. 5-HT2A agonists. NMDA antagonists. And… GLP-1 agonists.

spooky old-man-oracle voice: everything is pulmonaaaaryyyy

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Curious layman—is it possible that something in our environment has changed in the past several decades such that our bodies natural GLP-1 is not responding/present?

I look at the obesity epidemic, the efficacy of GLP-1, and wonder if the GLP-1 was once part of our body chemistry and, somehow, no longer is.

Or is the GLP-1 just a "magic bullet" that luckily works in a way to overcome our selfish desire to overeat unhealthy foods—there are other, non chemical, reasons we have been getting obese as a society over the past decades?

I've been on GLP-1 for a few months now and it is amazing. And I've been wondering this whole time—why did I previously have this "food noise" that, apparently, people like my wife do not? (Example: she'll often stop eating and say, "I'm full" when I'm thinking, that doesn't happen to me unless I eat an insane amount. Where is my I'm full detector?) I was sure thin as a rail for the first three decades of my life. Is it just a male, aging thing? ... I'm just flummoxed (but happy to be losing weight finally even if I do have to pay out of pocket every month for the drug).

I've had similar ideas for a while. That there's either a blocker of GLP-1 in our modern environment or something that previously produced or triggered production is missing.

I've not found any promising leads, besides maybe something fuzzy about intestinal microbiome. But I've not given up hope of figuring it out.

Especially, I'd note that if a food production company had accidentally added, say a GLP-1 antagonist (without knowing what it was) to their product, they'd just notice sales go up and consider it quite good business.

I personally don’t think it’s that complicated. I think it’s simply just the result of caloric density increasing as foods become engineered to make us want more. They’re saltier, sweeter, and generally more addictive. You can eat 2,000 calories in a sitting and not “feel full.”

Now, if you remove breads, sugars, and processed foods, try eating the same number of calories with whole foods only. You’ll become full way before you reach that number.

And some people, like your wife, simply respond to food differently. Id say she’s in the minority, though.

I, like yourself and most people, don’t feel full until I’ve eaten an unreasonable amount of certain types of foods. Since switching to Whole Foods and cutting out breads, sugars, and processed foods, I’ve lost weight while eating until I’m full/satisfied.

Stomach size is probably a massively under appreciated factor. If you naturally have a smaller build, you’ll likely have a smaller stomach, and that sense of being full will arrive much sooner.

Based on my experience fasting (as a huge guy) stomach size fluctuates quite a bit and is mostly conditioned on your eating habits. There have been times in my life where I could finish off a large pizza myself. These days I feel stuffed after one or two slices and a breadstick regardless of how little I’ve eaten during the day. Days I eat less I find I can eat less later. If I have breakfast (usually only ever on vacation) I can eat more later in the day before feeling full.

> I was sure thin as a rail for the first three decades of my life. Is it just a male, aging thing?

Yes?

When you hit the puberty your requirements go up for an additional 1000-1500 calories.

Women calorie demand returns back after puberty, men stays the same and the calorie burn rate (if you don't sit 24/7 at the screen ofc) are higher than a women' one in the first place. So you on all levels - including your own habits - are conditioned to eat a whole lot.

And then your forties come your body suddenly decides what you don't need that much energy and your metabolism slows down, winding down the calorie intake demands. But if all your life you needed a whole chicken with a plate to 'feel full' then you won't suddenly eat a couple of chicken wings and have a 'feel full' feeling.

And I would agree with a sibling comment: the food caloric density did increased a lot though 'saltier, sweeter, and generally more addictive' is not a rule but a more of a diet choices.

It's also possible that there has been an environmental or dietary "weight gain" effect for a really long time, but previous generations were counteracting it with cigarettes

It's hard to estimate how much the last couple of generations weight was because of smoking cigarettes suppressed appetite too

We live in a world of constant stress and noise and demands and (subtle and less subtle) violence and power games in basically all our relationships. No wonder our balance can only be (somewhat) restored by introducing massive amounts, either of “food” or “highly concentrated substances” like drugs. The village around us is out of balance, and burning, and so are we. Nowhere is (emotionally) safe, our nervous systems run on high intensity survival mode 24/7.

Yep; Things make much the same sense to me.

This paper is… I can't unsee it?: Aggression, Social Stress, and the Immune System in Humans and Animal Models – https://www.frontiersin.org/journals/behavioral-neuroscience...

serious paper, serious authors. Frontiers In is sometimes considered unserious? This is the real stuff.

Unserious tho: I lo-o-ove the Hideo Kojima-esque Friedman Brain Institute that one of the author is affiliated with, haha. <3

What naturally is supposed to produce GLP-1 in our bodies ?

It's important to remember that the natural GLP 1 you produce is a very very different molecule than GLP 1 agonists. The body uses natural GLP 1 in minutes. These drugs attach a very complex molecule to the GLP 1 site, allowing it to stay active there for hours.

So while your body produces it in a few places, the product gets used up almost immediately.

Keeping that in mind then, what processes do produce the (short lived) GLP 1?

It is produced naturally by the intestine and brain stem when food is present. It happens in response to fats, proteins, and carbs.

Eating high satiety foods

https://www.hsalist.org/tools/satiety-index/

That link is great, but putting jelly beans above peanuts makes zero sense to me, anecdotally. I can’t argue with the numbers/science but peanuts are something I reach for often when I’m looking to feel full, they are really great for that.

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