Tuesday, March 29, 2016

Stearate, butter and leptin receptors: Speculation!

I suppose the first thing I have to say is that the Tatter Paper of the last blog entry is not science in the form that any scientist might recognise. Control your variables is rule one... I only posted on it because, by a complete and apparently unplanned accident, the deep fried chips were of similar macros to the boiled mashed potatoes (BMP) but differed in fat type, in a manner very exciting from a Protons point of view. Just to emphasise: This was a chance gem in a pile of wallanga*. Picking the gem out of the wallanga can get your fingers dirty, but it's worth it. Chance is occasionally very useful.

I also happened to notice that, again by chance, the BMP macros were going to pan out somewhere near 40% fat, using butter as the bulk calorie source. This too is quite exciting.

Here are the BMP's macros, just roughed out to round numbers:

The post before the Tatter Paper post was merely pointing out that control C57Bl/6 mice do NOT become obese on their high (40% of calories, chance, neat huh?) fat diet in Ms Reeves' PhD. Their weight might be a little heavier on an olive oil based diet with generous PUFA and a little lighter on a stearic acid based diet with minimal PUFA, but nothing dramatic and absolutely no obesity in sight.

From the 40% fat fed mice in the stearic acid PhD:

Not a perfect match but reasonable. Why is this interesting?

My (repetitive) idea is that a certain amount of input to the ETC via ETFdh drives reverse electron flow through complex I to limit adipocyte distention. Stearic acid plus chow starch does this early during a meal. Butter plus potato starch does this early during a meal. Canola oil plus potato starch doesn't.

We have no idea whether the butter with potato starch would carry on, long term, to a slim phenotype in people. The long term effect of stearate is downwards and of oleate/linoleate is upwards on bodyweight in mice, but the effect is small. How come?

High level signalling.

Anyone who has read  Hyperlipid over the last few years will be well aware that I hate high level signalling. It usually takes a basic process, like the control of insulin signalling by the ratio of inputs at complex I, ETFdh and mtG3Pdh, and sticks a nice, glossy, superficial and somewhat opaque surface veneer over it. Then researchers can go off to find 25 or more genes which have some level of influence at some level of "higher-ness" of signalling above the core process. We then end up with a morass of over information with no one linking it all to the core process.

Such a high level signalling molecule is leptin. I have had relatively little interest in leptin over the years so may well be missing large chunks of information which are common knowledge to others on tinternet. The basic process seems to be that fat cells make leptin and the hypothalamus uses the information embedded in blood leptin levels to make a ton of decisions about energy homeostasis and energy use. Including appetite. Leptin secretion is related to adipocyte size but deeply under pinning adipocyte size is the ETC's control of insulin signalling, which sets cellular fat content. Leptin appears to provide some long term modulation of a series of repeated short term post prandial insulin events.

We can strip off the surface veneer of longer term leptin signalling from the core mitochondrial process by using db/db mice. The db/db mouse has non-functional leptin receptors. This means that the acute effect of mitochondrial signalling within adipocytes is not smoothed over or averaged out by the brain using leptin. The core process in fat cells takes over and can be seen via body weight and fat mass.

At peak energy flux stearic acid generates the maximum resistance to insulin's distending effect on adipocytes. Oleic/linoleic is far less able to generate insulin resistance to limit calorie ingress to each adipocyte.

The mice which are db/db homozygous become obese on chow (17% fat largely PUFA). On the 40% oleic/linoleic acid diet they become even more obese because they have plenty of dietary fat to store and a minimal ability to resist insulin's storage signalling. Stearic acid fed db/db mice also have a ton of fat available for storage. They don't lose any weight but they don't gain any weight either and they still up pretty damned close to normal mice fed normal chow. A little heavier, but not much:

The point of this post is emphasise that saturated fat, which I consider to drive physiological adipocyte insulin resistance, limits weight gain in leptin receptor KO mice. The fact it also cures their diabetes at the same time is another story.

Summary so far:

I consider that leptin smooths out the differences in fat storage produced by superoxide signalling originating from the ETC. I hate this, being a great fan of superoxide signalling. Stearate generated superoxide can largely offset the obesogenic effect of being a db/db mouse produced by the attendant lack of leptin signalling. It works with stearate at 40% of the diet, but not at 17% (elsewhere in the PhD).

The rest of this post is wild speculation originating from combining the Stearate PhD and the Tatter Paper:

Could this combo of spuds (or any other starch), butter (38% of calories, quite similar to 40% of calories from stearate) and meatballs work for people who are db/db in the same way as the stearate diet works in db/db mice?

Even more wild speculation, because the db/db genotype is fairly uncommon in humans:

Could the butter component of the "tatters" side-step failed leptin signalling (as in obesity) or relative/absolute hypoleptinaemia (as in the post-obese) in the same way that a ketogenic diet side steps the need for insulin signalling?

Further wild speculation:

Could putting a human on to a high saturated fat ketogenic diet sidestep most of the obesity problems currently prevalent in the world? By giving actual weight loss...

Make up your own mind...


A final comment on leptin. I'm unfamiliar with the massive complexity of leptin signalling. It seems to go on and on for ever. But just occasionally you come across little snippets of interest which suggest things about the function of leptin. There is a group who have developed an adipocyte specific leptin receptor knockout model. The only cells to lose their leptin receptors are the adipocytes. They still make leptin, they still release leptin, the liver still sees leptin, the hypothalamus still sees leptin. What happens?

"Despite a normal level of leptin receptors in the hypothalamus and normal food intake, mutant mice developed increased adiposity, decreased body temperature, hyperinsulinemia, hypertriglyceridemia, impaired glucose tolerance and insulin sensitivity, as well as elevated hepatic and skeletal muscle triglyceride levels".

The mice become obese and diabetic (on chow of course). Just by their adipocytes failing to perceive plasma leptin levels. And folks think the brain controls obesity! And of course you should be able to fix these adipocytes by supplying stearic acid as 40% of the diet.

Aside: The brain is clearly important in controlling all sorts of physiology. No one would deny this. Much as the computer of a modern car closely controls engine performance (my sister used to drive a Mitsubishi Lancer Evolution which turned out to develop 270bhp on a rolling road. She'd paid for the 315bhp version. Mitsubishi took out the computer, sent it to Japan for upgrade, refitted it and, hey presto, 315bhp. Never touched the engine), so too does the brain fine tune metabolism. But if metabolism is broken peripherally there's not much point looking in the brain. Trying to upgrade the performance of a Morris Minor by reprogramming its computer would be technically slightly difficult. When I used to tune Morris Minor engines computers still ran on punched cards. But the core process in the engines of a Lancer and a Moggy are the same. End aside.

So, did leptin arise to allow fat cells to monitor the fullness of other fat cells so as to maintain a reasonable level of fat stores? Then the brain started listening in? I don't know, but I find the idea interesting. And of course, the basic control of fat storage at that stage would then have been ETC derived superoxide. A little gets insulin signalling going. A lots shuts insulin signalling down. Insulin signalling, of course, is core. Even today.

Final final comment. This post makes me sound like Ray Peat. Something I find very embarrassing, to say the least.

About the asterisk:

*Wallang! Wallanga: You goin' in dat cave man? It's dark in there. We keep cows in there. We keep sheep in there. We keep pigs in there. Take care you don't step in no wallanga.

It needs a guitar, a folk club and a very long shaggy dog ballad to get you to this punch line.


karl said...

Now THAT is a fascinating leptin paper.. no need for trygly to block leptin at the BBB. I can think of it as sort of an 'auto-receptor'. (love this blog)

(Hmm.. your sister sounds interesting -- 315bhp ... I've sold equipment for making changes in ECUs (engine computers) so they could make real time changes while the car was running on a dynamo.. )

There are a couple of other reasons to focus on the local or cellular-level - ignoring the high-level signaling. First, I've tried to look at some of the hormonal bits - everything interacts with everything - what is an error signal for one part is a prime signal to another - stacked, nested control loops - then trying to understand what is a significant signal vs something to ignore. Looking at this from control-loop theory it is not humanly understandable - people that claim otherwise don't understand the question.

In electronics, we can use SPICE - to simulate nested feedback loops that interact non linearly and with convoluted loops. Sometimes the simulations fail to converge.. sometimes the simulations fool us. Just to create a similar tool for biology would take a whole lot more basic research (by real scientists - not grant-flow-practitioners). And then - it still can fool the user. ( Once your circuit is working in SPICE - it is MANDATORY to make a real circuit and see if it is true to life. We need cellular-level simulators working first... )

Another reason to stay focused on the cell-level is life worked when it was simpler - and the infrastructure for the most part is still there. The idea that we can understand the high level when our understanding of how the sub-components is not complete is foolish.

My quest to find a weight set-point led me to leptin - it looks like a good way to integrate a feedback signal. Now this bit has me thinking again... There is a point where if people get ever-fatter that the adipocytes divide - if we think of leptin on this cellular level - autoreceptor feedback - once fat cells divide, I'm having trouble imagining how it could go back.

So speculating further - what if people eat a high LA diet - get ever fatter - adipocytes divide - have they permanently changed their normal set point? Liposuction could reverse that - but only if LA exposure is limited in the future..

( I think of insulin as a feedback signal - and as in electronics, the amplitude of the feedback signal is often misleading - it is effected by the gain of the amp - ( insulin sensitivity) as much as the actual loop error signal. We have a paradigm in medicine where people think of low insulin sensitivity as the problem rather than the normal effect of having too much fat. If they work to prevent it - good chance they will harm people in the long run. )

The research where they have looked at the amount of LA in human body fat via NMR provides a research opportunity - is there a correlation between LA in human body fat and artery intima thickness? Or general obesity? Or cancer? (I really want to know the low-level why LA gets concentrated over time - I can imagine a couple ways, but don't think the magnitude fits - wonder if it has to do with the local-leptin signal?)

Peter said...

karl, yes, I feel lost in the high level signalling and there are UMPTEEN genes which can be knocked out to stop metabolic syndrome. Unfortunate, when I consider MS to be adaptive.... Liposuction gets you in to visceral vs peripheral fat. Pulling out sc fat leaves less adipocytes to take up calories and worsens MS. And visceral fat probably really does make matters worse, though the research here is messy, to say the very least.


Tucker Goodrich said...

"This post makes me sound like Ray Peat. Something I find very embarrassing, to say the least."

Yeah, he's certainly got some interesting stuff to say, and I've learned a lot from reading his stuff. But he comes to some unique conclusions, and I've not put the effort into following all his logic to see if they're valid.

But you could do worse...

raphi said...

Grant-flow-practitioners (as Karl calls them) like the heavy focus on higher level stuff because it's easier to argue everything & anything. The lower-level ETC stuff is much more constraining - hypotheses can be tested relatively quickly & destroyed soon thereafter (usually).

"So, did leptin arise to allow fat cells to monitor the fullness of other fat cells so as to maintain a reasonable level of fat stores? Then the brain started listening in?" ==> This question brings to my mind the idea of short-term & longER-term energy management. Tell me if this makes sense or if I've gone off the deep, speculative end of things:

Short-term adipocyte energy management occurs via superoxide signaling & longer-term management occurs through leptin signaling which - following from recent superoxide signaling patterns - regulates adipocyte size/number to predict upcoming energy availability. Am I postulating an unnecessary add-on or is such a short-term/long-term interplay sufficiently minimalistic?

Rattus said...

Ray Peat is great, and his articles are entertaining, but he does use a lot of analogies and random examples to illustrate his points, whereas Peter seems to focus more on the biochemistry. Not as flashy, but to quote Elon Musk:

"I think it is important to reason from first principles rather than by analogy. The normal way we conduct our lives is we reason by analogy. [When reasoning by analogy] we are doing this because it’s like something else that was done or it is like what other people are doing — slight iterations on a theme. First principles is kind of a physics way of looking at the world. You boil things down to the most fundamental truths and say, “What are we sure is true?” … and then reason up from there."

karl said...

@ Raphi

That's what I'm thinking - "brain started listening in" to a very old system. (I like the way you put it)

Long term/ short term / new trends all matter in feedback loops -

Proportional control is simple feedback - but to reduce the control loop error - we can feed back the integral of the error - to speed the loop response we can feed back the derivative of the error. And it sure looks like biology does tricks like this - ferinstance our eyes do a differential detection and the information that goes to the visual cortex is thus greatly compressed. ( look up the Retinex theory and further complications - there might be some holographic possess used in vision) - Biology does not have to understand what it is doing - it just has to work and be able to be preserved in our genes. )

A bit more of Feed back loops:

The understanding of feedback loops started with James Watt (yes, THAT James Watt) and after many people worked on it including Foucault - the need to understand it mathematically ended up with some work by Maxwell (yes THAT Maxwell - of the Maxwell equations - but this was just a side gig).

Biology does not have to understand what it is doing - just what ever works - thus we have a feed back loop that is on the edge of oscillation for insulin:


You also see negative feedback that is similar to electronics and can compensate for gains that vary and are non-linear functions.

Advanced control loops are nested and deal with loop filters - such as PID loops or the Kalman filter used in auto-pilots - ( that our brains can do something close to a Kalman filter is amazing ) - and I suspect that some of the maze of nested confounded endocrine loops are doing non obvious things as well.

So I wonder - is Is bipolar disease due to a broken control loop that is oscillating?
Or is leptin the integral term of a PID loop? Yet - medical biology seems to over simplify the topic, not realizing they are in over their heads - in material that I believe is well beyond human ability to simulate in our minds. Just understanding what is going on in a cell is utterly complex - is the fact that one thing effects the other important? - or do feed backs simply compensate the effect away?

George Henderson said...

Yes, leptin is hugely over-complex BUT leptin antagonises glucagon action in hepatocytes at a critical control point for glycaemia, just like insulin. Leptin action in parenchymal cells inhibits glycogenolysis and gluconeogenesis via decreased CAMP. That's got to be worth something. Post-prandial glycogen conservation is one of the immediate (low-hanging) fruits of carbohydrate avoidance.

Rattus said...

Also, Ray Peat's teeth all fell out and he wears false ones now, which he attributes to an "all wheat germ" diet he did at one point. I would guess the sugar probably plays a role as well. He was raised and homeschooled by extreme hippy parents, and I think this background made him open-minded to a fault.

Spittin'chips said...

I'm told, by the internet no less, that you can make mashed potato without butter or cream by adding diastatic malt powder. Provides a head start on the tato-to-glucose process, apparently, and...oh, shit, wrong blog.

Passthecream said...

@Chips :)

@Peter 'When I used to tune Morris Minor engines computers still ran on punched cards'

I love it when you talk greasy. (I had a vision of a system 360 cpu unit being towed by its cables behind an MM.)

'if metabolism is broken peripherally there's not much point looking in the brain.'

No sign yet of neuro surgery or mind altering drugs to fix t1dm, still the best-cheapest fix is peripheral insulin!

Peter said...

Pass, I programmed an IBM 360 for a year, East Midlands Electricity Board, using Cobol. Waaaay too big for towing by a MM, unless fitted with a Rover V8 engine I guess. I was so bad at programming that the look of relief on the group leader’s face as I handed notice was… I did better at Morris Minor and Mini tuning while I was at vet school.

Spittin’, a day early? Hee her hee.

@all, I guess at some stage I really will have to gen up on leptin. And there is clearly a role for higher level signalling, just it has to be in its place…


R Cobb said...

any comments on this current media storm ? Sorry for the long post..

Positive selection on a regulatory insertion-deletion polymorphism in FADS2 influences apparent endogenous synthesis of arachidonic acid
Kumar S.D. Kothapalli1,!,*, Kaixiong Ye2,!, Maithili S. Gadgil3, Susan E. Carlson4, Kimberly O. O’Brien1, Ji Yao Zhang1, Hui Gyu Park1, Kinsley Ojukwu1, James Zou1, Stephanie S. Hyon1, Kalpana S. Joshi3, Zhenglong Gu1, Alon Keinan2,* and J. Thomas Brenna1,*
+ Author Affiliations

1Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853 USA
2Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York 14853 USA
3Department of Biotechnology, Sinhgad College of Engineering, University of Pune, Pune, India
4Department of Dietetics and Nutrition, The University of Kansas, Kansas City, KS-66160
↵*Corresponding authors: J. Thomas Brenna, voice (607) 255-9182, fax (607) 255-1033, jtb4@cornell.edu;
↵Kumar S.D. Kothapalli, voice (607) 255-3831, fax (607) 255-1033, ksk25@cornell.edu;
↵Alon Keinan, voice (607) 254-1328, fax (607) 255-2323, ak735@cornell.edu
Long chain polyunsaturated fatty acids (LCPUFA) are bioactive components of membrane phospholipids and serve as substrates for signaling molecules. LCPUFA can be obtained directly from animal foods or synthesized endogenously from 18 carbon precursors via the FADS2 coded enzyme. Vegans rely almost exclusively on endogenous synthesis to generate LCPUFA and we hypothesized that an adaptive genetic polymorphism would confer advantage. The rs66698963 polymorphism, a 22 bp insertion-deletion within FADS2, is associated with basal FADS1 expression, and coordinated induction of FADS1 and FADS2 in vitro. Here we determined rs66698963 genotype frequencies from 234 individuals of a primarily vegetarian Indian population and 311 individuals from the U.S. A much higher I/I genotype frequency was found in Indians (68%) than in the U.S. (18%). Analysis using 1000 Genomes Project data confirmed our observation, revealing a global I/I genotype of 70% in South Asians, 53% in Africans, 29% in East Asians, and 17% in Europeans. Tests based on population divergence, site frequency spectrum and long-range haplotype consistently point to positive selection encompassing rs66698963 in South Asian, African and some East Asian populations. Basal plasma phospholipid arachidonic acid status was 8% greater in I/I compared to D/D individuals. The biochemical pathway product-precursor difference, arachidonic acid minus linoleic acid, was 31% and 13% greater for I/I and I/D compared to D/D, respectively. Our study is consistent with previous in vitro data suggesting that the insertion allele enhances n-6 LCPUFA synthesis and may confer an adaptive advantage in South Asians because of the traditional plant-based diet practice.

Passthecream said...

Milk products feature heavily in the vegetarian 'South Asian' diet.
Yoghurt, paneer, ghee...

ItsTheWooo said...

Very interesting peter, esp the anecdote about adipocyte LR knockout, phenotype is still largely like LR.

Leptin profoundly controls fat oxidation rate in tissues and I would venture to guess the abnormalities were induced by adipocytes failing to burn fat for energy secondary to the LR deficiency. This leads to systemic IR, and triglyceride deposits in other tissues. Also, with LR deficiency on adipocytes there will be a sympathetic deficit at the adiopcyte/beta adrenergic tone very necessary for burning fat, which might account for the lower body temp. Speculation.

It would be interesting to see how LR mutant humans respond to a high stearate diet; I'm skeptical it would work but would love to see the outcome. Leptin deficient humans are easily treated with leptin, and I suspect most cases of minor leptin insufficiency such as weight loss pts would agree being slightly fatter than you would like is better than eating 1 fatty acid only lol.

We have almost opposite views re: top and bottom processes. Its rather like describing the engineering of a car, vs describing travel plans. We can talk about how the engine works, how it is constructed. We can also consider one's mental intent to drive slowly or drive quickly with the machine, utilizing the same engine discussed previously. The machine, based on heirarichal actors (driver) can be modified to change behavior; it can go very slow, use physical forces more to move like hills, and conserve gas. It can speed and burn it up quickly. THe engine is the same in both contexts but heirarichal actors result in a total different machine function.

This is why , IMO, leptin and hierarchical adipocyte regulatory controls are most important. Ultimately, a lot of the things we are describing re: SFA, superoxide generation, adipocyte IR ... leptin profoundly influences how this occurs at all.

But i agree an understanding of both is important! For better/best disease treatments however , favorably altering the higher actors in some way is probably more productive.

Passthecream said...

Hi Woo, intersting what youre saying there.

Analogies,,, some of us unfortunately have engines rather a lot like the MM mentioned before - 798 cc four cylinder sidevalve with a thermosiphon cooling system in a heavy body with no seatbelts, and no matter how hard you push the acelerator it just doesn't go any faster except downhill because the brakes aren't very good either. Every ounce of physical performance needs to be teased out, fuel additives, timing, sports air filter, gt stripes, etc.

I know I'm in dangerous wonky metaphor territory here but metab. is so complex that humans have to zoom in to various sub-sections and work out models of what they do, then how you might solder various bits together and zoom out to see what happens. Im not sure if it really is possible to think of this as hierarchical, my idea is that it is all system-dynamic, given what Karl says that some variables/signals have far reaching consequences. Everytime i think i have a handle on some part, some cycle or feedback loop, danged if someone with a bigger engine doesn't come along and throw a spanner in my understanding.

Peter, a PDP-8 on the back seat might do the job. Unfortunately I sold mine to a collector about the same time i gave away my last MM so I can't perform the experiment atm.

karl said...


Analogies pretty much always miss lead to some extent. But - if we speculate on an evolutionary basis - the early cells had a system that works internal to the cell. Later the brain listens in and other systems then interact. What is important to realize is that there are two layers that both do the same thing. The "why" matters. Why are the earlier functions conserved?

Single point genetic errors happen, and if there are duplicitous overlapping control systems, the organism survives to pass on it's genes. This is the rule rather than the exception.

When I looked into thyroid systems - again there are multiple feed back systems - all interacting with the control - thus all responding to each other. When we look at one bit of the system isolated - what we see is likely to be confounded by what we are missing. Are the correlations due to a primary control - or the feedback of another mechanism. It is a fantastically muddy mess that can easily lead to false assumptions. The bits that are discovered first tend to be thought of as more important - but the truth is in the big picture they all matter - it is the total system.

It does not mean that the high level systems are not important - ( I think leptin and the autonomic nervous system both REALY matter ). But constraining ones efforts to the cellular level, as Petro is doing helps remove some of the noise and perhaps lets us see further ahead.

There are no end of possible causation at the high level - ferinstance - We know that LA messes with neurons - so does LA produce a type of neuropathy that reduces the autonomic nervous systems effect on adipocytes? Quite possible, but clear knowledge of what is happening at the cell level with β3 and β2 adrenergic receptors in adipocytes (both brown and white) seems like the best starting point.

The constraint helps keep us from unknowingly living in some ungrounded theory. Without the focusing effect of the constraint we end up grabbing onto bits that may or may not matter ( yes - there is an effect - but is it important with the backdrop of redundant control systems? - Does a 5% significant effect matter in the big picture? Is the feed back linear? --- It becomes like nailing Jell-O to the wall )

"A bad analogy is like a leaky screwdriver"

Re: PDP-8 --Actually, an 8-bit 6809 could do the job if it was written in assembly language. Some of the early ECUs were nothing more than a very lame custom 8096 with a bunch of interrupt timers tacked on..

Peter said...

Woo and karl, my feeling is that when the high level control systems are broken there is the possibility of working at the most basic levels of metabolic control to bodge the job. Trying to work with what can be done at the mitochondrial level. The concept of trying to feed ob/ob or db/db humans on cocoa butter would be interesting, to say the least. In part the problems would go back to adipocyte PUFA content and the problems of fatty acid turnover in adipocytes again. Who knows. My feeling for the rats in the PhD is that the result was quite, but not completely, unexpected. There are a whole series of interesting things about these mice, especially the low O2 consumption and the low temp. They're still db/db. How did they feel? On ad lib they limited calories. They become normoglycaemic. But it was already a too long and too speculative post, so....

I’m slogging through the insulin high level pathways as regurgitated in http://www.ncbi.nlm.nih.gov/pubmed/26967715 by Williams and Wu but it’s hard without the ondansetron. It’s a massive compilation of every high level signalling pathway relating to insulin and insulin resistance, I guess you’ve got it. They understand nothing, just nothing. Unfortunately they have some bits and pieces about NOX4 and H2O2 that I’ve been working at for several months now so, every now and then, I go back and have a read. They’re full of statements that are almost, but not quite, true. They remind me of our bestest friend in obesity research.

Pass and karl, 1098s all the way I’m afraid. Five MMs in all. With a 998 mini thrown in to which I fitted a 1098 engine from a Morris 1100. Then another, after that one gave up too. I wasn’t very kind to my cars! The guys at the Board who knew what they were doing were trained in Assembler and, to sort out my worst cockups, they went to machine code in the dump and usually found where I’d divided by zero…….

R Cobb, not really. Evolution will favour the best of a bad job I guess.


Passthecream said...

High level control: I don't know what the implications are exactly but one of my co-workers still has a stable prolactinoma after having had his pittuitary removed due to cancer some years ago. He gets very weak when he catches a cold etc but otherwise no problems, fully functional. Probably wouldn't survive very well on a lc diet.


(1098cc - LUXURY!)

David Leitner said...

Peter: Thank you for sharing your explorations. I have request that is somewhat off-topic. Do you think some folks are predisposed to do better eating a higher percentage of MUFAs rather than SFAs, even on a well-formulated HF diet?

If you have time, could you share what you think of this study: "A high intake of saturated fatty acids strengthens the association between the fat mass and obesity-associated gene and BMI." http://www.ncbi.nlm.nih.gov/pubmed/22049296 ?

I seem to be doing mostly well on a high-fat, and high sat-fat, diet, although I carry more body fat than I would like. I wonder if I shouldn't switch to more MUFAs due to the fact that I am rs1121980(T;T), with a 2.76-fold increased risk for obesity particularly with saturated fat (according to http://www.ncbi.nlm.nih.gov/pubmed/22457394).

Peter said...

Hi David,

I think it would be perhaps a little rash to ever base a decision on associations observed in data from FFQs. That would seem to be accepting causality from a set of recalls, a possible mistake in its own right, in which neither trans fat nor fructose get a mention in the current paper. And, of course, weight is only a number. I don't think anyone has looked at a simple comparison of SAT vs MUFA in a LCHF setting directly, so you have to wonder what effect the switch might have on numbers like HbA1c. It's clearly not going to help distant surrogates of health such as HDL, for which MUFA are "neutral" and SAT are "good". The db/db rats suggest MUFA might make you fat, even if it's just via the PUFA which contaminate most MUFA.


Peter said...

Mice, not rats!

Jack Kruse said...

Sunlight and leptin, and sunlight and cold and leptin are the feedback loops you all need to focus on. There is a NADH is a fluorphore protein (340nm UV ) at cytochrome 1 redox couple. What happens at this couple needs to be properly yoked at the leptin receptors in the hypothalamus fed light info from the SCN.

karl said...

@jack Kruse
Can you link to a paper?

I read someplace that besides Vit-D there were 10 other photo-chemicals produced in the skin. Never could find the paper where this might have come from.

There is also a lot of correlative crap with vit-D - yes sick people have a lower level - but is it because they are inside because they are sick?

And what is the effect of sunshine vs supplements? When vit-D is made - it also reduces 7-dehydrocholesterol - does that have an effect?

I bought a couple of dermatology text books trying to find what we know about photochemistry in the skin - I don't think we know much at all.

Rattus said...


Random question, but when I asked you about sucrose before, in reference to why it might cause issues, you said "Fructose enters glycolysis w/o regulation." Do you think the same is true for galactose. Is it also unregulated? I notice the same issues from lactose as I do from sucrose, perhaps worse. It's not an intolerance thing, as it happens within minutes of consumption.

Peter said...

Hi Rattus,

Probably not. Galactose converts to glucose-1-phosphate then glucose-6-phosphate, upstream of the control point at phosphofructokinase whereas, in the liver, fructose enters glycolysis through aldolase to give dihydroxyacetone phosphate and glycaeraldehyde, well below the main control step. Not sure what the problems might be from galactose for you…


Rattus said...


I was assuming the problem was lactose, as that was the only commonality that would link the symptoms. Didn't think to blame the protein or fat in dairy, as cheese doesn't seem to be a problem, except for Gjetost, a Swedish cheese with a very high lactose content [was trying to use it to get carbs from dairy instead of starch, to see what would happen. Didn't go well]. Perhaps it is just the additional CHO, and nothing unique to lactose, but starch never seems to be as much of an issue. I drink cream every day, no problem. Cheese, no problem. But milk, yogurt, etc...not good.

I was thinking that maybe the fat, protein, and lactose in dairy all have a synergistic effect that does something to insulin, maybe because it is designed to grow baby cows? I dunno. Bodybuilders cite milk as number one growth food.

Passthecream said...

Rattus, there is a list of natural cow hormones which may be present in raw milk about half way down this page:


Perhaps one or more of them persist in some of those milk products? Is gjetost the cheese made from the milk of newly lactating cows?