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Comment by AnthonBerg

10 hours ago

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

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 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.

  • 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 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.

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.