"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.
Peter
