Saturday, May 29, 2021

Random musings on uncoupling (2) revised

Okay, here is how I ended the last post:

"It's also worth pointing out that this appears to be an ancient system and that high PUFA exposure might uncouple in anticipation of the cellular caloric influx which PUFA signify. It has become pre emptive and has, certainly in rodents, largely been shifted from "all" cells primarily to the brown adipose tissue. The PUFA signal might also be very central to the browning of white adipose tissue to beige. That's a process you would never want to have to use, being in a situation where generating beige adipose tissue might be helpful is not somewhere you want to go."

which is wooly thinking, to say the least.

Uncoupling is triggered by ROS generation using a locally available PUFA derived lipoxide signal combined with whatever fatty acids are available in the immediate vicinity of the mitochonrial inner membrane uncoupling proteins. A supply of PUFA is absolutely needed for the signalling molecule generation (4-HNE and related) and intact PUFA have been selected to uncouple better than saturated fats do. These features might be related.

PUFA are always present in the inner mitochondrial and have many functions. this function of acting as a safety valve appears to be one of them. It will not need to be specifically linked to bulk PUFA induced cellular caloric excess. I envisage it as a response to any excess caloric ingress, hyperglycaemia or markedly elevated FFAs post prandially (or even elevated levels of systemic fructose) when the law of mass action (ie a large concentration gradient) overwhelms the normal response of insulin resistance when cells are replete.

I view this aspect as the ancient system. It applies to any caloric overload and happens to use a PUFA/ROS signal to limit excessive mitochondrial membrane potential using uncoupling.

The fact that this system is functional at levels of PUFA intake far in excess of those that a particular species (humans) might be adapted to is perhaps unexpected but does seem to be the case, but this is more understandable if it is viewed as a generic safety mechanism.

Whether those slim rodent models consuming 45% of their calories as linoleic acid are dealing with excess caloric ingress by uncoupling or whether they are actually under caloric deficit because the emergency uncoupling system is being activated inappropriately due to oversupply of signalling precursors/uncoupling facilitating fatty acids is not clear.



cavenewt said...

Thanks for expanding on that, Peter. It helps.

Peter said...

Hopefully it makes some sense now!


Passthecream said...

Funny considering what I just suggested to la_bob in a previous posting! I feel like an echo. ( A very faint and distorted echo)

Almost but not quite unrelated: I'm about to cook up a batch of linseed oil varnish and have been checking up on some lipid chemistry. I will be heating LSO up around 230 to 240c Palmitic and stearic acids have boiling points up around 360c, palmitic 351 and ala a massive 443c but that good heart healthy linoleic acid boils as low as 230c. That's impressively different and some indication of its reactivity.

Justin said...

Pass, I have been thinking of running some of these oils through my packed bed deposit rig I use for motor oil. I run the clamshell heaters at 250c. That's interesting that ALA has a boiling point of 443c. I would have never guessed that. I run the sludge rig at 150c and run it through a 3.5 micron filter. That would be an interesting experiment too. All lines and fittings would definitely need to be initially heated if running individual saturated fatty acid components though. Lol

cavenewt said...

Linseed oil is great stuff. My floors are adobe mud finished with linseed oil, which polymerizes over a few months and turns into, essentially, linoleum. I spent yesterday painting linseed oil onto a clay plaster windowsill. It has admirable qualities which, somehow, don't seem appropriate for incorporation into living organisms.

Passthecream said...

Linoleum is a great example of a biodegradable made from renewables and you can get a liquid, pour-on version now. Heavily oxidised LSO is the core ingredient == linoxyn.

Justin, when you take raw LSO to 240 or so it froths a bit and something separates out. The remaining pale oil is a non-catalysed rapid drying oil. I think it's just hydrolysis, separation of glycerol but I can't quite work it out.

To bring this back on topic, cooked PUFA start doing that in iron cookware and continue doing it as they course through your system creating havoc. You get a lipoperoxidation cascade.

Martin Sip said...

"ala a massive 443c but that good heart healthy linoleic acid boils as low as 230c. That's impressively different and some indication of its reactivity."

Pass, I expect ALA with 3 double bonds to be more reactive (oxidatively unstable) than LA with 2. Boiling point is more about intermolecular interaction which are heavily influenced by shape than molecular reactivity IMO.

Justin said...

Martin Sip, yep. One should not confuse reactivity with volitility or vise versa.

Passthecream said...

True but that's a lot of thermal energy zipping around near its boiling point. I did wonder briefly if it would be good for deep frying! It was a surprise anyway.