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Experimental Fat Loss's avatar

I'm doing ex150 right now, so your wish will come true and we will find out haha.

Agreed on the "complicated," it really depends on what the mechanism even is. Is it that cells built w/ excess PUFAs don't burn energy good and send bad signals? Then it might depend on which type of cells we're talking about. Brain cells reacting to leptin? Other brain cells? Cells producing leptin? Mitrochondria? Mitochondria of which cells?

It's probably not actually the RBC phospholipids.

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John Lawrence Aspden's avatar

> I'm doing ex150 right now, so your wish will come true and we will find out haha.

OK, since I believe that protein is somehow directly involved in this hypothesised set-point-shifting, I will boldly predict that your slight increase in protein intake will lead to a slightly raised set-point, which will result in just enough extra hunger to cause your weight to go up a few pounds, probably in an exponential-decay sort of pattern.

And then if you go back to ex115 afterwards, that will reverse and you'll go back to where you are now. (Or maybe a bit lower because of two more months of PUFA-clearing)

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John Lawrence Aspden's avatar

RBC phospholipids themselves are probably not that interesting. RBCs are pretty inert. In mammals they don't even have a nucleus so I don't think there's much going on there at all. They might just be little bags.

Excess PUFAs in the membranes might shorten the lifetime of the cells by oxidising or something, but they might also make them a bit more flexible so they squeeze through capillaries easier and mean the heart doesn't have to work so hard to pump them through a damaged circulatory system.

I'm more interested in the PUFA levels in the serum (the bit of blood that isn't cells) and in the various fat-transport lipoproteins. That stuff's getting everywhere and could be doing lots of bad things.

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Experimental Fat Loss's avatar

Agreed, RBC is just an easy to measure proxy. We're the drunk man looking for his linoleic acid under the streetlight.

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John Lawrence Aspden's avatar

> Is it that cells built w/ excess PUFAs don't burn energy good and send bad signals?

Could be both. Metabolism is probably borked everywhere because of PUFAs clogging the works just by being the wrong fuel.

And if you're a cell whose metabolism's not working properly then probably everything you do is affected, including, if you're a fat cell, things like generating the appropriate amount of leptin for the amount of fat you contain.

> Brain cells reacting to leptin? Other brain cells?

Again all of that is going to be affected by a metabolism that's not generating enough ATP to power the systems, or enough Krebs-cycle-intermediates to funnel off to actually construct the systems in the first place.

But it could also be that the PUFAs are themselves acting as signalling molecules and interacting with actual receptors, either stimulating them as if they were the real ligands, or binding to the receptors and stopping them working, or binding to the receptors and making them fire too much. Each effect there is going to be complicated in itself, and also exactly the sort of thing that's different from person to person precisely because it's never mattered before. There are hints in the literature that that can happen with leptin receptors.

But there also seem to be direct effects of PUFAs on the activities of various enzymes and pathways. The cancer people seem pretty confident that omega-3 PUFAs act directly on mTOR, the thingy that works out when it's time for a cell to divide, so essentially PUFAs are acting like rapamycin, a natural fungicide that also works on animals and plants. That's terrifying! No wonder the bloody things are "anti-inflammatory". They're paralysing your immune system.

And also at least in liver cells, PUFAs seem to interfere with glycolysis. Again that's going to be a sort of general metabolic derangement that affects everything.

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