Periorbital Fat Gain Theorised Mechanism

[frankramsey]

Bimatoprost causes periorbital fat loss by causing a condition known as prostaglandin-associated periorbitopathy. This happens because Bimatoprost is an analogue PGF-2alpha which inhibits adipogenesis.

Surely, then, by applying a PGF-2alpha antagonist to the area we could inhibit the inhibition of adipogenesis and thus promote adipogenesis. AL‐8810 and AL‐3138 are competitive and non-competitive inhibitors of the PGF-2alpha receptor (their structure is simply a fluorinated analogue of PGF-2a)

These compounds can be bought via various sites at fairly high prices - although some of their syntheses may be very manageable.
e.g. https://www.medchemexpress.com/al-8...nfX23H92enehxrxj1zZOrc5Uw7LXfUx3Uthh9_Z-ZPy5V

Unfortunately, the periorbitopathy caused by bimatoprost seems to be short-lived and only lasts for the duration of the treatment. To me this implies that a PGF-2alpha antagonist would have a similarly short lived effect and at a price point of roughly 250dollars/mg, filler, implants and grafts seem like the best alternative.

 

[vincentzygo]

theres a good thread on this already i think

 

[Bryce]

theres a good thread on this already i think

You mean to tell me a grey recycled an old idea and condescended it without formatting? No way

 

[vincentzygo]

is this it?

FIX YOUR DISGUSTING UNDER-EYE AREA WITH PIOGLITAZONE + OLEIC ACID

The Bootleg Biohacker Serum for People Who Look Like Sleep-Deprived Divorcees WHAT ARE WE FIXING? Your under-eyes looking like a niglet with no under-eye support We’re going to obliterate: Puffy orbital fat that swells like you’re allergic to good choices Sagging, deflated skin from...

looksmax.org

 

[vincentzygo]

You mean to tell me a grey recycled an old idea and condescended it without formatting? No way

he seems sentient

 

[jeoyw9192]

is this it?

FIX YOUR DISGUSTING UNDER-EYE AREA WITH PIOGLITAZONE + OLEIC ACID

The Bootleg Biohacker Serum for People Who Look Like Sleep-Deprived Divorcees WHAT ARE WE FIXING? Your under-eyes looking like a niglet with no under-eye support We’re going to obliterate: Puffy orbital fat that swells like you’re allergic to good choices Sagging, deflated skin from...

looksmax.org

In theory it should work but sourcing and formulating the solution is quite difficult, also not sure if anyone actually tried it if they did happen to get it

 

[frankramsey]

You mean to tell me a grey recycled an old idea and condescended it without formatting? No way

I did not know that a thread for this already exists - apologies - I searched for PGF2a in the search bar in the top right and could only fin stuff about hair growth and nothing about PAP.

he seems sentient

Appreciated - I am a med student hence why ik some terminology without using this account much.

 

[Bryce]

I did not know that a thread for this already exists - apologies - I searched for PGF2a in the search bar in the top right and could only fin stuff about hair growth and nothing about PAP.

Appreciated - I am a med student hence why ik some terminology without using this account much.

Nevermind he's sentient

 

[jeoyw9192]

I did not know that a thread for this already exists - apologies - I searched for PGF2a in the search bar in the top right and could only fin stuff about hair growth and nothing about PAP.

Appreciated - I am a med student hence why ik some terminology without using this account much.

Hey man, curious if you've seen this subreddit before: https://www.reddit.com/r/estrogel/. There are a few threads on related topics (e.g., potentially locally stimulating fat)

 

[frankramsey]

Hey man, curious if you've seen this subreddit before: https://www.reddit.com/r/estrogel/. There are a few threads on related topics (e.g., potentially locally stimulating fat)

Never seen this subreddit before although will check it out.

Nevermind he's sentient

In theory it should work but sourcing and formulating the solution is quite difficult, also not sure if anyone actually tried it if they did happen to get it

The thread that @jeoyw9192 references utilises a different MoA that I am suggesting. Both have the end result of promoting adipogenesis, but so does stuffing your face with cookies so I don't think I've plagiarized anybody elses work.

If you want the generic names for the mechanisms

Referenced Thread: Nuclear Receptor Agonism (Peroxisome Proliferator-Activated Receptor gamma)
My Thread: Alarm Chemical Antagonism (PGF2a)

 

[jeoyw9192]

Never seen this subreddit before although will check it out.


The thread that @jeoyw9192 references utilises a different MoA that I am suggesting. Both have the end result of promoting adipogenesis, but so does stuffing your face with cookies so I don't think I've plagiarized anybody elses work.

If you want the generic names for the mechanisms

Referenced Thread: Nuclear Receptor Agonism (Peroxisome Proliferator-Activated Receptor gamma)
My Thread: Alarm Chemical Antagonism (PGF2a)

very interesting though I'll admit I'm not too knowledgable on the specifics behind the mechanisms, so I'll definitely read into it more. Though I guess I take it from what you've said the effects would be somewhat temporary? whats the duration if it would theoretically work?

 

[frankramsey]

very interesting though I'll admit I'm not too knowledgable on the specifics behind the mechanisms, so I'll definitely read into it more. Though I guess I take it from what you've said the effects would be somewhat temporary? whats the duration if it would theoretically work?

Evidence concerning the reversibility of the fat gain/loss is fairly anecdotal from what I can tell. It has been known for full reversal and no reversal to occur. The degree of reversal seems to correlate inversely with the duration of use (as one might expect).

A problem with my MoA is that I'm inhibiting the inhibition of adipogenesis, not promoting it. This means that it is perfectly possible for no change to occur.

There seem to be ways of making it cheaper. i.e. a 5mg sample of AL-8810 from Cayman Chemical is listed at $459, which is still over $90/mg.

Fillers still seem to mog in terms of cost effectiveness


A grey question I have though is about eyelid pulling or like pulling the skin on the orbital bone. I don't see why this wouldn't work? Are the results unnatural? Are there well-documented results?

 

[Ogionth]

Bimatoprost causes periorbital fat loss by causing a condition known as prostaglandin-associated periorbitopathy. This happens because Bimatoprost is an analogue PGF-2alpha which inhibits adipogenesis.

Surely, then, by applying a PGF-2alpha antagonist to the area we could inhibit the inhibition of adipogenesis and thus promote adipogenesis. AL‐8810 and AL‐3138 are competitive and non-competitive inhibitors of the PGF-2alpha receptor (their structure is simply a fluorinated analogue of PGF-2a)

These compounds can be bought via various sites at fairly high prices - although some of their syntheses may be very manageable.
e.g. https://www.medchemexpress.com/al-8...nfX23H92enehxrxj1zZOrc5Uw7LXfUx3Uthh9_Z-ZPy5V

Unfortunately, the periorbitopathy caused by bimatoprost seems to be short-lived and only lasts for the duration of the treatment. To me this implies that a PGF-2alpha antagonist would have a similarly short lived effect and at a price point of roughly 250dollars/mg, filler, implants and grafts seem like the best alternative.

Except that the baseline levels of PGF₂α near the periorbitals under normal conditions are trace, unless there's inflammation etc so even in theory, this will not work, because if you intentionally introduce PGF₂α for this then you're just "creating a problem" and then solving it, you're not making improvement.

 

[Ogionth]

A grey question I have though is about eyelid pulling or like pulling the skin on the orbital bone. I don't see why this wouldn't work? Are the results unnatural? Are there well-documented results?

Because the skin is viscoelastic, unless you're actually damaging the collagen and elastic fibers, the skin will go back to the original position.

And if you damage it by pulling it enough, then the body will try to heal it and you'll just get an unaesthetic result.

You're not really increasing regional adiposity (which is what is needed for the aesthetic result) by pulling lol

 

[jeoyw9192]

Because the skin is viscoelastic, unless you're actually damaging the collagen and elastic fibers, the skin will go back to the original position.

And if you damage it by pulling it enough, then the body will try to heal it and you'll just get an unaesthetic result.

You're not really increasing regional adiposity (which is what is needed for the aesthetic result) by pulling lol

Fat grafting/fillers it is then?

 

[frankramsey]

Except that the baseline levels of PGF₂α near the periorbitals under normal conditions are trace, unless there's inflammation etc so even in theory, this will not work, because if you intentionally introduce PGF₂α for this then you're just "creating a problem" and then solving it, you're not making improvement.

I wasn't suggesting increasing the baseline levels of PGF2alpha lol. Although, my proposed mechanism would be most effective if a patient was undergoing a bimatoprost treatment. I was suggesting to use it as a monotherapy to prevent binding to the orbital FP prostanoid receptors.

Because the skin is viscoelastic, unless you're actually damaging the collagen and elastic fibers, the skin will go back to the original position.

And if you damage it by pulling it enough, then the body will try to heal it and you'll just get an unaesthetic result.

You're not really increasing regional adiposity (which is what is needed for the aesthetic result) by pulling lol

high iq - thanks for information. Although, my goal was not to increase the adiposity by this method (because that obviously wouldn't work lol) but just to sort of stick the looser skin to my upper eyelid using tape which becomes easier after stretching it.

Fat grafting/fillers it is then?

Yeah unless you wanna try this: https://looksmax.org/threads/fix-yo...ye-area-with-pioglitazone-oleic-acid.1412164/ which I haven't looked into yet.

 

[Ogionth]

Fat grafting/fillers it is then?

Fillers to that region, no.

Fat grafting, yes.

 

[jeoyw9192]

I wasn't suggesting increasing the baseline levels of PGF2alpha lol. Although, my proposed mechanism would be most effective if a patient was undergoing a bimatoprost treatment. I was suggesting to use it as a monotherapy to prevent binding to the orbital FP prostanoid receptors.

high iq - thanks for information. Although, my goal was not to increase the adiposity by this method (because that obviously wouldn't work lol) but just to sort of stick the looser skin to my upper eyelid using tape which becomes easier after stretching it.

Yeah unless you wanna try this: https://looksmax.org/threads/fix-yo...ye-area-with-pioglitazone-oleic-acid.1412164/ which I haven't looked into yet.

Yeah I've seen that thread before, think I bumped it before. It seems quite promising of course, unfortunately no anecdotes. What do you think about that thread @Ogionth https://looksmax.org/threads/fix-yo...ye-area-with-pioglitazone-oleic-acid.1412164/

 

[Ogionth]

I wasn't suggesting increasing the baseline levels of PGF2alpha lol. Although, my proposed mechanism would be most effective if a patient was undergoing a bimatoprost treatment. I was suggesting to use it as a monotherapy to prevent binding to the orbital FP prostanoid receptors.

No one said you were suggesting it but the only way it would even matter is if either the baseline levels were high or they were artifically made high, and I cleared both the possibilities.

And no, your proposed mechanism would be pretty much useless due to the ROI even when patients are on bimatoprost and regardless, that would have nothing to do with looksmaxxing anyway at that point.

high iq - thanks for information. Although, my goal was not to increase the adiposity by this method (because that obviously wouldn't work lol) but just to sort of stick the looser skin to my upper eyelid using tape which becomes easier after stretching it.

Welcome, mate

 

[frankramsey]

No one said you were suggesting it

The statement here:

because if you intentionally introduce PGF₂α for this then you're just "creating a problem" and then solving it, you're not making improvement.

made me think that you misunderstood my post.

even when patients are on bimatoprost

I'd dispute this - I don't see why it wouldn't help with PAP.

Although I don't dispute that the method is unlikely to yield good results (as I clarified in the first post of this thread) as compared to filler etc unless somebody can find a way to synthesise a PGF2alpha antagonist for dirt cheap - then it would be worth a punt imo.

 

[Ogionth]

The statement here:

made me think that you misunderstood my post.

That's okay

I'd dispute this - I don't see why it wouldn't help with PAP.

I never said it wouldn't, I said it's not feasible due to the ROI and the fact that it won't be a looksmax since bimatoprost is not really a good looksmax unless you're taking very careful measures to apply it and doing it indefinitely.

Do you have dyslexia? Genuinely curious atp This is the second time you're miscontruing what I say.

Although I don't dispute that the method is unlikely to yield good results (as I clarified in the first post of this thread) as compared to filler etc unless somebody can find a way to synthesise a PGF2alpha antagonist for dirt cheap - then it would be worth a punt imo.

It won't, as I said unless you're intentionally creating a problem and solving it back (one possibility) and in the other possibility, there's just not enough PGF₂α to antagonize in the first place to make a difference, the levels being produced are trace.

You can try but it doesn't even work in theory.

 

[Ogionth]

Yeah I've seen that thread before, think I bumped it before. It seems quite promising of course, unfortunately no anecdotes. What do you think about that thread @Ogionth https://looksmax.org/threads/fix-yo...ye-area-with-pioglitazone-oleic-acid.1412164/

Might read later

Formatting looks bad.

 

[frankramsey]

Ogionth, thanks for the clarification.

I agree that the ROI for using a PGF₂α antagonist as a standalone treatment is poor due to the trace baseline levels you mentioned. My initial post was more of a theoretical exploration of the mechanism, and I fully acknowledge that it's not a practical solution given the current cost and the mechanism of action.

Regarding the comments on my post, I took your statement about "creating a problem and solving it" to be a misunderstanding of my proposal, which I felt was a valid point to correct. As for your final question, I'm not dyslexic, but I apologize if my replies have been unclear. I'll be more precise in the future.

The discussion has been insightful, and I appreciate the feedback. It's clear that fat grafting remains the most viable, albeit invasive, option for this aesthetic concern.


(I'm better at chess tho)