Sunday, November 18, 2012

Protons: Physiological insulin resistance

Woody emailed me a pdf of this venerable paper. I like it. Even though it was generated in-house by Proctor and Gamble!

The core findings are that if you eat a diet with around 60% of calories from fat, then you end up lighter if that diet is based on safflower oil (omega 6 PUFA) and heavier if it's based on lard. Here's the table:

Well, there you go!

Safflower oil is more ketogenic than lard. It also allows greater fat loss during 72 hours of starvation, 10.3g of fat loss from safflower fed rats vs 3.9g from lard fed animals, here we are:

Mmmmmmmm, linoleic acid, the elixir of life and Weight Watchers' friend. And I thought it was obesogenic!

So what does the small print say? Lots!

First thing to make my ears prick up is that during the whole study the rats were only allowed to eat for 2 hours a day, in a single solid block. That means they were force fasted for 22 hours a day. We've noted from Table 3 that safflower oil allows greater weight loss under fasting conditions. So is it any surprise that the safflower rats ended up at 195g vs the 222g of the lard fed rats after eight weeks of this intermittent fasting? I'll come back to why in a moment.

In contrast most modern papers show that linoleic acid, the primary component of safflower oil, is grossly and transgenerationally obesogenic...

But that's because there is a difference between ad lib feeding and 22h per day forced fasting!

The difference is in the glucose levels. Look at these graphs from Fig 1, especially the glucose levels in the middle top graph:

Now, far be it for me to put words in to the mouth of a lab rat, but which group of rats is the hungriest? Which group becomes most hypoglycaemic perhaps? Even Dr You-are-confused-man-Guyenet seems to have, in an aberrant moment of lucidity, a glimmering of perception that hypoglycaemia makes you hungry. Or should I say drives eating behaviour? Did I ever even mention gluttony? If you are force fasted for 22h you can't overeat. You can't even eat to your metabolic needs without accessing significant amounts of stored fat.

Under full starvation a rat lives off of its fat. If linoleic acid is what is being released from the adipocytes under fasting conditions it provides significantly less FADH2 relative to NADH in to the electron transport chain of all fat burning cells than the mix of fatty acids from the adipocytes of lard fed rats. ie there is less physiological insulin resistance. This failure means you fail to keep glucose levels normal during starvation. Let's rub that in: Failure to develop physiological insulin resistance during starvation results in hypoglycaemia and hunger.

Exactly the same will happen in any soy oil fed USA citizen. The end result will still be the failure to develop the essential physiological insulin resistance which is needed to keep blood glucose normal during fasting.

When the average soy oil fattened American is asleep they HAVE to, finally, stop snacking on carbohydrate crap, which is the only way they can maintain a decent blood glucose level. At this time blood glucose falls, simply because their muscles stay insulin sensitive and glucose falls in to them. The brain will not accept hypoglycaemia. Some time, in the middle of the night, there has to be a Refrigerator Raid.

And, OMG, they eat calories! And calories count! Did I ever mention gluttony? Or, perhaps, is the Refrigerator Raid simple physiology?

The 22h daily fasted rats have a locked refrigerator. However hungry they feel due to hypoglycaemia, they are not getting any extra food. But why is there extra weight loss under starvation? Insulin was tricky to measure from a rat in the 1970s, but I know that the safflower loaded then starved rats had the lowest insulin as they are both insulin sensitive and hypoglycaemic. Low insulin = more lipolysis = more ketones and more weight loss. Logical.

Now let's go a step further. Blood glucose is low. It's low because the F:N ratio of linoleic acid is low and that's what is being released from adipocytes. This is metabolism. Individual cell by individual cell, it's a metabolic phenomenon. Picked up by the brain as hypoglycaemia.

Hypoglycaemia must drive food intake to avoid cerebral catastrophe. Glucose is not a neurotransmitter per se. The hypoglycaemia has to be converted to a neurotransmitter based message to affect behaviour. Oddly enough, a derivative of linoleic acid is a neurotransmitter. Linoleic acid is the parent molecule of the endocannabinoids. Even the cleanest nosed obesity researcher has heard of the munchies. Wouldn't it be funny if eating linoleic acid messed with your blood glucose level and this hypoglycaemia triggered the production of endocanabinoids from, you guessed, the parent molecule (of the hypoglycaemia!), linoleic acid within the brain? The same molecule which triggers the hypoglycaemia, making the hunger essential, in the first place.

You could view it as linoleic acid ingestion is a signal that hypoglycaemia is in the offing. If random evolution was looking for a substance to "choose" as a neurotransmitter to deal with hypoglycaemia, it might just be simplest to modify the basic lipid which is most prone to trigger low blood glucose throughout the body in the first place... You could then end up thinking that the endocannabinoids "just happen" to control appetite as a primary function. Of course, once the control system is in place you are all set to mess with it by demonising saturated fat and pushing corn and soy oils.

Well, I find the concept hysterical. But then I find most brain centred obesity research pretty amusing.



Purposelessness said...

This is pretty straight-up. Lard is just more rewarding, dontcha know?

Margaretrc said...

Pretty awesome work, Peter. But then your work always is. Thank you! Bookmarking for when this study hits the news (if it does) and the headlines read"Lose more weight with Safflower oil than lard."

Edward Edmonds said...

I must be reading to much Jung lately. Last night I was reading through the rest of your posts on physiological insulin resistance and then this morning a new one.

I'd expect FBG to rise higher with long term high-fat consumption. I'd have a tendency to think that if it didn't that means someone is cheating... I'm thinking a rising FBG is like a highway where all the people are perfect drivers going to their appropriate destinations and taking the correct exits and not getting lost i.e. this is an effect of increasing efficiency.

karl said...

If rats have about a 6x metabolic rate - would it be wrong to assume that 22 hours of fasting would be similar to 132hours for a human? or an 11 day fast?

Gadfly said...

Does this mean there's a "metabolic advantage" to safflower oil that defies CICO? ;)

Puddleg said...

raiding the refrigerator - this was a condition called "night starvation' in the days before fridges.
It was a made-up condition then probably (nige on night starvation: ) but satisfying it has turned it into a real monster...

Bill said...

Dietary linoleic acid elevates endogenous 2-AG and anandamide and induces obesity (

Peter said...

Purposelessness, Ah!

Margaret, bit late for a 1975 paper now!

Edward, ta for the heads up, addendum is up.

Karl, yes, 22 hours is a long time for a rat and its adipocytes are insulin resistant quite quickly. I had a link some where in one of the posts on the premature reports of the demise of the insulin hypothesis of obesity but can't remember which...

Gadfly, I'm a CICO person, I just don't think we measure well enough to see where the metabolic advantage calories go. They go somewhere! Somewhere OUT.

George, well I never!

Bill, they measured linoleic acid in everything except adipose tissue. These clowns crack me up. They still don't know if caloric loss in to adipocytes triggered the rise in endocanabinoids or whether the overloading of the brain supply of arachidonic acid forced overfeeding. How do you tell? Simple overeating requires insulin resistance to deal with caloric overload through this overeating. Caloric loss in to adipocytes secondary to linoleic acid accumulation in them causes increased insulin sensitivity. The added complication is the fact that linoleic acid increases insulin sensitivity per se. Makes my head go round.

But the paper is by people so focused on the brain that they don't even consider adipocyte fat composition worth analysing (if it's the paper I'm thinking of).


DLS said...

mmm, interesting findings!( eats a huge bag of salted peanuts roasted in vegetable oil, a bucket of ice cream coated with awesome hfcs liquids , big chicken , and 200 gr of sugary chocolate... in that order... remains super lean. im starting to feel fructose and pufa makes no frigging difference... i still eat meat, cheese and 10 yolks- gmo soy fed- most days... and also drink liters of supermarket milk, (insuliinnnsss)but most days im eatin whatever the hell i want. no damage so far. a year. maybe is the fasting?

DLS said...
This comment has been removed by the author.
DLS said...

also, i had a bunch of potatoes mixed with oily mayo with that chicken! and the chicken was fried... in vegetable oil! ( and i bet they used that rancid oil multiple times, koss i ate this in a old gas station in the middle of nowhere ) also road trip so no activity at all, just sitting for 30 hrs . fasting... ah lately im doing lots of cereal with the milk. awesome.

DLS said...

and chocolate every day... ok ill stop now, continue the space talk

Scott Russell said...

One thing I've noticed about people who intermittently fast is that they are all rather obsessed with food. Night starvation, perhaps?

DLS said...

or maybe is just projection, as in that's your on inability to fast cope with hunger speaking.. yes i love to eat but also im never hungry. (and if that was the case, so be it,just a signal that i fuked somehow, solution? just eat more. never happens..) anyway im able to enjoy eating any kind of food like nobody else i know, with no ill consequence. try going on without food for a few days. then 23- 25 hrs is just a friggin joke, it just happens. i never think about food m mainly self obsessed thats all ;)

Scott Russell said...

Never tried continually fasting for more than 14 or so hours, so I guess I cant really talk. I've seen many people follow Leangains become food obsessed, but then again that often couples fasting with caloric restriction.

As a side note, fasting means your body is running on palmitate 90% of the time. A nice F/N ration there. Might be the fasting is a band-aid over an otherwise broken eating style. Or maybe you're just lucky.