If it enhances autophagy through AMPK it should not be limited to mitophagy but also cover xeno-autophagy

Good point. That might make it helpful for fighting infections.

@CrumblingCookie said in Peaty uncoupler vs. Ozempic who wins ? New study.:

So a shift away from carbohydrates to FAO

People often paint uncouplers as FAO-increasers. But they increase FAO and carb oxidation.
The above article mentions it increasing TCA cycle, which can be fed by carbs and fat.
It probably also depends on which tissues we are talking about. If you want to lean out your liver increasing FAO there is probably a good thing.

@CrumblingCookie said in Peaty uncoupler vs. Ozempic who wins ? New study.:

The MOA of BAM15 would then be a combination of inducing UCP and something along the line of metformin or berberine or spermidine (but lacking the Beclin-1 upregulation).
(A comparison with resveratrol is less suitable since, although it lowers intracellular ATP through AMPK, I dare say its most important effect is through Sirt1)

AMPK increases SIRT1.
So BAM15 should do that, too.

BAM15 improved hepatic lipid metabolism disorders by enhancing mitochondrial autophagy through activation of the 5'-AMP-activated protein kinase (AMPK) pathway. This indicates that BAM15 could be used to treat liver lipid metabolism issues and offers a solid theoretical foundation for managing lipid-related diseases."

If it enhances autophagy through AMPK it should not be limited to mitophagy but also cover xeno-autophagy. And of course the lipophagy, as they write. The only other drug which I know of which has been used to ease fatty liver or intracellular lipid accumulations are carbamazepine over a course of several months or hydroxy-beta-cyclodextrin per mucosal uptake (takes a looong time) or by injection. Since carbamazepine is quite some shite on the brain for many, they should look further into BAM15 for those affected by genetic lipid-accumulation defects.
It also ranks in BAM15 into the caloric restriction mimetics range of autophagy-inducers. So a shift away from carbohydrates to FAO and potentially even beneficial effects on the mechanisms of innate immunity for intracellular pathogen clearance, which by itself can greatly improve cellular functioning by ridding it of amassed (auto)phagosomes.

The MOA of BAM15 would then be a combination of inducing UCP and something along the line of metformin or berberine or spermidine (but lacking the Beclin-1 upregulation).
(A comparison with resveratrol is less suitable since, although it lowers intracellular ATP through AMPK, I dare say its most important effect is through Sirt1)

"N5,N6-bis(2-Fluorophenyl)-[1,2,5]oxadiazolo[3,4-b]pyrazine-5,6-diamine (BAM15) is a recently identified mitochondrial uncoupler with antitumor, anti-inflammatory, antioxidant and antiobesity properties. Although it has been shown that BAM15 has a high targeting ability to the liver, its capacity to improve liver metabolic disorders and the underlying mechanisms are not well understood. This study examined how BAM15 works in high-fat-diet (HFD) induced obese mice. Our results showed that compared with 2,4-Dinitrophenol (DNP) and carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP), BAM15 has a higher binding capacity and stronger activity in mediating proton uncoupling, and effectively promoted mitochondrial fusion, division, autophagy, and the tricarboxylic acid cycle. BAM15 improved hepatic lipid metabolism disorders by enhancing mitochondrial autophagy through activation of the 5'-AMP-activated protein kinase (AMPK) pathway. This indicates that BAM15 could be used to treat liver lipid metabolism issues and offers a solid theoretical foundation for managing lipid-related diseases."

https://pubmed.ncbi.nlm.nih.gov/41527408/

I'll definitely do another round at some point. But I don't really have weight to loose, so it would be more for the other benefits.

I'd also be willing to sell a part of it to someone in Europe.

It might not sound like much but 600g per week is 2,4kg a month , that's pretty decent without trying hard.

Hi, please let us know how this continued in your experience. It's been two months. Have you lost 4.8kg and gained strength?

https://pmc.ncbi.nlm.nih.gov/articles/PMC11113268/

If you can’t find that, a higher fat milk with honey would also do the trick

Have you tried upping your evening calories? Icecream before bed has healed me more than a lot of hacks out there.

That could be, I do eat like 6 eggs a week

These are rookie numbers. You've got to pump these numbers up! You may need those 6 eggs = c. 900mg choline not per week but per every day! Go Go egg pudding!

Feeling initial benefits from substances until soon hitting a wall is easy. The art lies in figuring out and overcoming the latter. I, however, have more imminent priorities than upping metabolism rn.

That could be, I do eat like 6 eggs a week so I should be getting enough choline. But maybe the b vitamins are the issue or insomnia isn't related to BAM at all.

I'll maybe try 50mg over the weekend. i could also see myself using it weekly for the weight and liver benefits just to make if easier to maintain weight or eat more without gaining.
There is also an androgenic feeling to it.

If you or someone else wants to try it, im willing to sell half of it to bring the cost down .

I have lost about 600g in weight and my strength has increased. I was stuck at 8 pull ups for a few months and on my last day of taking it I increased the dose to 35mg and I was able to do 9 pull ups.
If my observation holds true, and there is some evidence for that in the studies I posted, than this will become VERY popular amongst bodybuilders. A safer version of DNP where you loose weight and maybe even increase strength ?!
The first 4-5 days I had a lot of bile dumps, what seems to be candida. I have noticed the same with DNP. Maybe uncoupling somehow helps the liver/ gallbladder somehow to excrete fungi.
I also noticed from day 1 that I felt warmer and my hands were slightly sweaty. Although measured ear temp didn't change.
I have stopped after a week because insomnia seems to have creeped up on me, but I'm not sure at all if it's even related because it's still there after I stopped.

Overall those results are quite amazing given that a normal dose seems to be around 200-400mg and I noticed all of this from 25-35 mg.

On its safety:

https://pmc.ncbi.nlm.nih.gov/articles/PMC7338798/#emmm202012088-fig-0005ev

BAM down regulated SCD1 by almost 900-fold ! SCD1 concerts saturated fats into unsaturated fats and is implicated in many chronic diseases.

"...severe downregulation of sterol regulatory element‐binding transcription factor 1 (Srebf1 ; 490‐fold downregulated), carbohydrate‐responsive element‐binding protein (Mlxlpl ; 99‐fold downregulated), fatty acid synthase (Fasn ; 89‐fold downregulated), stearoyl‐CoA desaturase (Scd1 ; 898‐fold downregulated), adipose triglyceride lipase (Pnpla2 ; undetected in BAM15), and peroxisome proliferator‐activated receptor gamma (Pparg ; undetected in BAM15)”

I think this above part is very interesting. These down regulated factors all point to BAM lowering lipogenesis. It might even all be downstream from PPARg .
Fireinabottle writes about it here . Animals that lack PPARg remain insulin sensitive on a high PUFA diet and gain less weight. This happens because PPARg increased PDK4 which lowers pyruvate dehydrogenase. So lowering it will increase pyruvate dehydrogenase and enable you to burn sugar better.
In the study above on BAM15, PPARg was undetectable.

"BAM15 reduced atherosclerotic plaque formation, lipid deposition, and inflammation, and diminished mtROS expression and ox-mtDNA content in the AS mouse models. In both in vivo and in vitro experiments, BAM15 markedly inhibited the activation of the NLRP3 inflammasome, leading to reduced pyroptosis in endothelial cells. "
https://pubmed.ncbi.nlm.nih.gov/40393254/

Here, BAM15 and a Trb agonist are more effective for treating fatty liver than each on their own. So combining BAM with sobetirome or just T3 should be good combo for the liver .
https://pubmed.ncbi.nlm.nih.gov/39152636/