Thursday, September 05, 2019

Hyperlipid Protons ambassadors

Many people may have noticed that the blog Hyperlipid is not exactly the most user friendly of blogs. The prose clearly appears to make sense but some of the concepts are not always particularly simple unless you have the Protons idea well understood.

Last year (2018) Mike Eades made a sterling presentation which summarised the concept in a talk at Low Carb Down Under in terms that were much more accessible



and Brad Marshall now has a blog on which, throughout 2019, he has been writing around ideas which derive partly from the Protons thread on Hyperlipid. But in significantly more user friendly language, while still being on the spot.

Fire in a Bottle

is his website, a very neat name. It's good. He farms low PUFA pigs too.

Peter

*Very few things in life are quite so disappointing as finding that insulin interacts directly with the NOX4 (NADH oxidase 4) complex to generate the bulk of the initiating low levels of superoxide/H2O2 which trigger insulin signalling. Some ROS do come from the electron transport chain but NOX4 seems rather important. Sigh. Bulk ROS to terminate/blunt insulin signalling do appear to be ETC derived...

19 comments:

Noclue said...

Link to Fire In a Bottle is broken.

Wout Mertens said...

That link should be https://fireinabottle.net/about-fire-in-a-bottle/

Peter said...

Thanks, fixed

Peter

cavenewt said...

Just watched the Michael Eades video. I finally understand reverse electron transport! If anyone finds an unhurried version of this talk, please post a link.

John said...

Small world, i live in the same village as Brad Marshall and have been to his farm for a field day. He had a straw bale house on the property that had been partially eaten (by goats we later discovered) but at the time we were imagining the three little pigs story come to life.

For anyone interested in his ideas about avoiding corn and soy feed to raise low PUFA pork, you can find his other blog by googling 'revolution pig'. Interesting stuff.

Bob said...

I agree with cavenewt. Dr Eades's presentation really doesn't do the Protons concept justice. It's just too difficult to cram so much complex information into less than 45 minutes. It helped me immensely that I have read the Protons thread (most of it more than once) and already understood RET. A newcomer to the concept would still be baffled. I give Eades much credit for trying.

Sometime back I thought to try what Brad Marshall has done. Peter needs some simplifying for less technical audiences. I'm just a layman, so Marshall with his science background is a better choice for the job. Still Marshall could use some editing help, and I might just offer.

One of the great things about Hyperlipid is that it attracts some technically-oriented or otherwise well-read commenters (George Henderson, Karl, Raphi, Melchior, itsthewooo, Passthecream, Tucker Goodrich, Heretic, others) who really add some meat (pun intended).

I'm glad Brad Marshall alerted Peter to his blog. And I'm glad Peter thought enough of it to respond in kind.

bill said...

Does this presentation by Dr. Frank Shallenberger
fit in with your protons series? He talks about
NAD/NADH.
https://www.youtube.com/watch?v=85EPbiABqJs&feature=youtu.be

altavista said...

Off-topic but Pablo Kelly is still going, and from that pic, with Seyfried I think, going strong.

https://m.facebook.com/pablosbrainjourney/posts/2327270010855323?refsrc=http%3A%2F%2Fpablosjourneythroughbraincancer.wordpress.com%2F

Michael Eades said...

@Peter

Thanks for posting the video. And thank for the kind words.

@cavenewt

I was allotted 30 minutes for the talk. It ran long, and I knew it, so I was hurrying. The organizer of the event was in the first row right in front of me and was getting agitated. I probably shouldn't have tried to cram so much info into such a short talk.

BradAtFireInABottle said...

Hey Peter!

Thanks for the link.

Hey Bob, obviously I'm writing nights and weekends and there's a lot of material to cover. Any editing help would be greatly appreciated!

brad at fireinabottle d0t net

Brad

Peter said...

Hi all,

Mike and Brad, you are both very welcome. The concept of trying to distill the Protons concept in to 30 minutes is a challenge, to say the least. When I started I only had the haziest of ideas about where NADH and FADH2 inputed to the ETC and this took some time to get my head around. And once you start talking about electron transporting flavoprotein and its mitochondrial dehydrogenase you are already waaaaay out of almost everyone’s comfort zone….

bill, he’s more in to NADH:NAD+ ratios as a cell signalling cascade. Depletion of NAD+ and/or excess of NADH is a Bad Thing. Hence the interest in NAD+ precursors as longevity drugs (and anticancer drugs, as in Abraham Hoffer and associated posts somewhere on Hyperlipid). Not so sure about the ozone concept. Protons is largely about ROS and control of insulin signalling both acutely and in the longer term.

Peter

ctviggen said...

I watch very few videos (no time, can't watch at work, etc.), but the Dr. Eades video I thought was great, though I also have read a lot of the Protons thread.

Peter, are you familiar with Gabor Erdosi? I saw a Twitter thread with Gabor (@gerdosi) and Amber O'Hearn (@KetoCarnivore) where Gabor said that other effects might override the Protons effect.

Here's the tweet:

Gabor Erdosi �������� (@gerdosi) tweeted at 0:24 PM on Tue, Aug 13, 2019:
And what does an insulin sensitive fat cell mean? One would think enhanced lipid storage, but proper leptin and adrenergic signaling results in browning and increased lipid oxidation rather than storage. Unless you block it eith other factors, such as leptin insensitivity.
(https://twitter.com/gerdosi/status/1161312513448992773?s=03)

The follow up tweet from Amber:

L. Amber O'Hearn (@KetoCarnivore) tweeted at 0:27 PM on Tue, Aug 13, 2019:
Sorry to ask you to repeat yourself, but I want to make sure I'm hearing you right. Are you saying that with proper leptin and adrenergic signalling, adipose insulin sensitivity results in browning and and lipid oxidation rather than storage?
(https://twitter.com/KetoCarnivore/status/1161313404881031168?s=03)

Gabor answers "Yes, precisely. That's part of the homeostatic machinery of weight reduction. The fallacy is that excess fuel has to be stored."

That's the extent of my Twitter knowledge (lucky to find this!).

It would be interesting to see a conversation between you and Gabor about this subject matter.

cavenewt said...

@Michael Eades

My comment was absolutely not a criticism! The animation of reverse electron transport finally got it through my head how that works, and whetted my appetite for more. I would love to know if you ever do a more relaxed version of this presentation.

shitmypresidentsays said...

Thanks for the great blog and linking Dr. Eades. What would the F:N ratio of MCT oil be? I'm not smart enough to figure it out :-).
Would it be good to cook with and use as a salad dressing?

Michael Eades said...

Hey @cavenewt,

I didn't take it as a criticism at all. Due to my time constraints, I felt rushed. I had to fight not sounding like one of those audiobooks set to 2X normal speed. :)

The whole protons idea doesn't make much sense unless you understand just how much linoleic acid has been added to the diet during the time the obesity epidemic has evolved. I felt like I had to take the time to provide that evidence as a prelude before really getting into the protons part of the talk.

Bob said...

Dr Eades said, "The whole protons idea doesn't make much sense unless you understand just how much linoleic acid has been added to the diet during the time the obesity epidemic has evolved."

That's a great point, an important point, and it was, in fact, your "new hypothesis of obesity".

Like cavenewt, I'm not running down your presentation. Not at all. You tell a good story and tell it well. I just think there are at least half-a-dozen presentations there, some of which are "brick-making" (fundamentals of the ETC, inputs from the Krebs cycle, RET and ROS, and so on), and some of which are "consequences" (insulin resistance, PUFA obesity, and so on).

Maybe the key is to convince conference organizers this (low-level physiology) is important and schedule presentations accordingly. But, at least you got it out there, and interested folks can always come to Hyperlipid for the details.

And at least you didn't sound like a chipmunk when you spoke at 2X normal speed!

Peter said...

MCTs are close to palmitate. I wrote this a long time ago

Palmitate 0.48
C8 caprylic 0.47, chosen by peroxisomes to hand to mitochondria
Palmitoleic 0.45

I think oleate would be around .46, can't find this at the moment

I guess it's OK. I do always wonder why physiology goes to such lengths to divert MCT directly to the liver and then convert them to ketones as a matter of some priority. An interesting are to speculate in...

Peter

Peter said...

Hi ctviggen, Yes, I did see that interchange and I note the caveats. I also took a brief look around at browning or beiging of adipose tissue and the feeling in obesity research is that it might indeed be a physiological attempt to limit further weight gain. In particular it is a feature more of visceral adipose tissue than subcutaneous adipose tissue, visceral adipose tissue being the most sensitive to insulin. These folks from Italy https://www.ncbi.nlm.nih.gov/pubmed/31440209 have some nice comments

“we suggest that an increased REE and browning in metabolically complicated severe obesity could represent an effort to counteract further weight gain”

so yes, homeostasis kicking in. The down side is how humans appear to achieve browning of white adipose tissue, ignoring potential drug therapies. I would suggest the physiology is triggered by massive obesity, although the term physiology might be better replaced by pathology…

“Our results clearly showed that UCP1-VAT expression was significantly increased in severe human obesity (BMI > 50 kg/m2) and that it behaved as an independent predictor of REE”

How important insulin driving browning is at a BMI under 25kg/m2 is hard for me to fathom.

How do you get to a BMI of >50kg/m2 in the first place? Pathological adipocyte insulin sensitivity derived from PUFA oxidation failing to induce insulin resistance as adipocytes fill and chronically elevated insulin from excess carbohydrates acting on those hypersensitive adipocytes. Caloric loss in to adipocytes drives hunger through the ventromedial hypothalmic neurons. These sense the loss of calories in to adipocytes as a hypocaloric state so trigger hunger, more eating and more dietary fat loss in to adipocytes. Weight gain is a calorie loss phenomenon, as far as the brain is concerned.

Browning as a late development seems less important to me. Browning looks like the adipocytes are deciding they do actually have too many calories, irrespective of what the brain thinks.

Just my musing...

Peter

karl said...

Ok - I sent the link to Eades' video to my wife and kids - they have been giving me a hard time about me looking at and talking about women's legs not looking right - and LA.. Now I have company - Eades.

Actually, I think most of the public's skin looks a bit inflamed - the line between adipocytes and immune system seems really blurry to me.

Not a bad primer on NAD:NADH -

If this catches on - say in 40 years - might be common knowledge??

False narratives can live a long time..