Tuesday, February 18, 2020

CPT1aL479 resurfaces nicely

Originally from Erik Arnesen, via a retweet by Miki Ben-dor:

Inuit metabolism revisited: what drove the selective sweep of CPT1a L479?

as in

Coconuts and Cornstarch in the Arctic?

The P479L gene for CPT-1a and fatty acid oxidation

The abstract looks very nice, I can't wait to get hold of the full text!


Edit: The paper is long and somewhat repetitive. There is a much neater paper from Amber which people might enjoy:

Evidence on chronic ketosis in traditional Arctic populations

End edit.


Amber O'Hearn said...

Wow. She really ought to have cited me, as I've published some of these same arguments. https://escholarship.org/uc/item/8wz5h9kp

Peter said...

Mea cupla Amber, I missed your publication too.

Your's looks to be the more concise version!


Tucker Goodrich said...

Yes, Amber's is less repetitive, for sure.

I don't find this paper's argument particularly compelling, as:

1. There's no evidence that a high protein diet would shut down fat oxidation and ketosis. The fact that the Inuit survived to get this mutation (whatever its purpose) suggests that high protein did not shut down fat ox.

2. The notion that this mutation is somehow glucose sparing is never adequately explained. Ketones are glucose sparing. This mutation shifting away from ketone production should enhance the requirement for glucose, or be accompanied by higher fat oxidation in places that currently depend on glucose/ketones, like the brain. She doesn't offer any evidence that this takes place.

3. My thought was that this might be an adaptation to allow great fat ox., in concert with less-coupled mitochondria, for heat generation. However this doesn't appear to be the case.

"...the preserved coupling in muscle tissue suggests evolutionary selection for conservation of energy over heat production at the level of muscle mitochondria despite the extreme cold of the arctic winter."

"Mitochondrial coupling and capacity of oxidative phosphorylation in skeletal muscle of Inuit and Caucasians in the arctic winter"


Peter said...

Nice paper Tucker. Certainly makes uncoupling drop well down the list of explanations for the L497 mutant. I realise they didn't state the CPT1a phenotype but the Inuit individuals studied were certainly very northern and very coastal so... A nice idea sunk by hard data. So it should be, if that's the case.

I loved the trichinella antibody prevalence comment.


DLS said...

gibberish @ mumbo jumbo... context its all: super low temperatures, super high solar UV radiation, super low carb, super high pufa shit, super high protein = hiper high stress resulting in regular high cortisol and constant hunger. so yes no ketosis doh. is impossible to fast under such extreme hard conditions, this is why people look old and wrinkled. they are getting kfed hard. da end

Passthecream said...

When the news of the discovery of that mutation hit the presses there was a merciful release from the Innuit diet/ lifestyle being held up as one of the exemplars of how we should eat. Evolutionary reality hit back hard, some palaeo food bloggers got egg on their faces and it was quiet for a while, I kept hoping that the Kitavans, Masai, Ainu et al would follow suit and be left in peace. It seems to me, Weston Price excepted, that this falls into a paradigm similar to the concept of the Noble Savage, many strands of the Palaeo diet being especially egregious examples of cultural revisionism and outright romantic fantasy. Well, we all do like historical re-enactment and escapism and we certainly need interesting speculations and observations to break us away from the death-grip of the agro-industrial lifestyle but it can end up in some very bad and disrespectful places ...


Amber O'Hearn said...

Yes, nice paper, Tucker. I hadn't seen that.

I'm a little surprised by the hypothesis, because if the presumption is that you've already got a challenge getting fat into the mitochondria, then it would seem strange to suggest that it could then also be spared for more uses. But it looks like they didn't mention CPT1A at all, so maybe they were just looking for something independent of that. Which would make sense, actually, since CPT1A is specifically hepatic, not muscular.

One way I had been thinking that thermogenesis could maybe be an advantage of reduced CPT1A, is if the rate limit it imposed forced more fat to be oxidised in the peroxisomes, which might result in more uncoupling there instead of in the mitochondria. But again maybe that would only makes sense if there were mutations in adipocyte pathways.

My paper had to be concise because it was supposed to be an "extended abstract". :-)