Mouse study.... Maybe they have found the protein key to the inflammation response to fat. Maybe someday, there will be a drug.

Oh, fodder!

Here, we see that a high fat diet, when given to humans, makes them leaner, not fatter:
http://forum.lowcarber.org/showthread.php?t=402590

Furthermore, all the markers for health, and disease, were better for the high fat diet, than for any other diet. So, my question is, how come TLR4 is inactive in humans? Since obviously, the more fat we eat, the more TLR4 should be active, and the more inflammation there should be, right? Maybe it's not TLR4 that turns on inflammation in humans after all. Maybe it's not fat either.

Hmmm, weird. When I started eating a high-fat diet I lost 45 pounds.

Perhaps you don't have a mouse metabolism?

I think I'm not a normal mouse.

I like that. We are the normal ones. LOL

More exactly determining metabolic pathways is real science. It likely will have no consequences until several other steps are also determined. I really don't understand the snarky comments which always seem to be the response to articles like this.

ps - we are right not to expect real world results from these studies in the short term

Lewis Carroll ended the poem, "Hunting of the Snark" with

"In the midst of the word he was trying to say,
In the midst of his laughter and glee,
He had softly and suddenly vanished away __
For the Snark was a Boojum, you see.

that kind study always angers me.

they just NEVER say if they're doing a HF-LC or a HF-HC diet.

Big news...

They aren't doing a DIET study.

There is more to life than diet studies, there is basic PHYSIOLOGY, for example, which is what the study was about.

I can understand your frustration. Not all diet related studies are classic diet studies. Some are for basic understanding of processes, not just results you can apply tomorrow morning, or afternoon.

i didn't mean it was a study about dieting ; but my point is, the PHYSIOLOGY is completely different in HC and LC. i could understand a high (unrefined unprocessed) carb woe to be healthy, with LOW, healthy fats OR a HF-LC woe to be healthy, but not a HF-HC, exept for a growing child.

so when they only mention "high fat", i am very very frustated indeed. what type/quality of fats ? what quantity/type/quality of carbs ? what amount of proteins ?

????

Well, I find this interesting. Think about it, though. The fatty acids that the body are 'mistaking for invaders' are obviously not ALL fatty acids, or a higher fat low carb diet would be a disaster instead of salvation for most. Fat ingested through the diet, as well as ingested and environmental toxins, can store as triglycerides in the human body, right. So what if it's just certain kinds of fat, and/or fat when affected by certain other chemicals, that causes this response? For example, eating mostly O6 fats with almost no O3/O9s, or eating trans-fats, or eating those fats with certain other things -- it's not beyond the realm of possible that this may cause a 'type' of fat storage that the body itself reacts badly to.

Or what if toxins in fat in a certain quantity trigger the perception of invader?

I think it's a very interesting question. However I think that 'inflammation' is a condition which causes the growth of adiposity in the first place -- not just a condition which reacts to it.

Vitamin d-directed rheostatic regulation of monocyte antibacterial responses.The active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)(2)D) enhances innate immunity by inducing the cathelicidin antimicrobial peptide (hCAP).
In monocytes/macrophages, this occurs primarily in response to activation of TLR, that induce expression of the vitamin D receptor and localized synthesis of 1,25(OH)(2)D from precursor 25-hydroxyvitamin D(3) (25OHD).
To clarify the relationship between vitamin D and innate immunity, we assessed changes in hCAP expression in vivo and ex vivo in human subjects attending a bone clinic.
Of these, 38% were vitamin D-insufficient (<75 nM 25OHD) and received supplementation with vitamin D (50,000 IU vitamin D(2) twice weekly for 5 wk).
Baseline 25OHD status or vitamin D supplementation had no effect on circulating levels of hCAP.
Therefore, ex vivo changes in hCAP for each subject were assessed using peripheral blood monocytes cultured with 10% autologous serum.
Under these vitamin D "insufficient" conditions the TLR2/1 ligand 19 kDa lipopeptide or the TLR4 ligand LPS, monocytes showed increased expression of the vitamin D-activating enzyme CYP27b1 (5- and 5.5-fold, respectively, both p < 0.01) but decreased expression of hCAP mRNA (10-fold and 30-fold, both p < 0.001).
Following treatment with 19 kDa, expression of hCAP: 1) correlated with 25OHD levels in serum culture supplements (R = 0.649, p < 0.001); 2) was significantly enhanced by exogenous 25OHD (5 nM); and 3) was significantly enhanced with serum from vivo vitamin D-supplemented patients.
These data suggest that a key role of vitamin D in innate immunity is to maintain localized production of antibacterial hCAP following TLR activation of monocytes.

Of course everyone here knows the obvious that being fat soluble Vitamin D is carried in fat molecules and when those fat molecules are stored in fat cells so the vitamin d is also locked up. Fat people are VITAMIN D DEFICIENT because the Vitamin D they make doesn't circulate it's imprisoned in their fat cells, that is why it isn't available to fight TLR4. That is why people have to be told to use EFFECTIVE AMOUNTS 1000iu/D3/DAILY for each 25lbs weight.

I don't suppose the idea of correcting vitamin D insufficiency will occur to any researcher as an alternative to developing a TLR4 blocking drug that could sell for a lot more money than the $15 it takes to stay vitamin d replete through the year.

Hutchinson, would you mind summarizing that abstract in lay language?

Also, the figure of 1000iu/D3/DAILY for each 25lbs weight seems high. I take only 2000IU daily, and my Vit. D. serum levels came back from 25 to 55, which is normal.

Antimicrobial peptides and the skin immune defense system The full text of this paper is online and that will give you are start in understanding how the immune system works.

But for most people it takes 5000~6000iu to get around 60ng/ml. The heavier you are the more proinflammatory cytokines you produce and the greater the inflammatory burden so the MORE vitamin D3 you require. Also the body senses how large your stores are and progressively wastes increasing amounts of D3 so it's more responsive the lower your 25(OH)D status and less responsive the higher your 25(OH)D level. That is why we know 10,000iu/daily is a safe upper limit even in sunny places.

The adverse consequences of being below 50ng/ml are such that it is safer to suggest people use an amount that is likely to be effective and meet their needs in full than to understate the amount and have them fall short.
It's not as if there is a significant difference in cost between 2000iu and 5000iu supplements.
2000iu daily in the UK will leave everyone who takes just that amount still vitamin d deficient. In my view it is dangerously misguided to suggest any amount that you know will fail MOST of the population.
As no one can be harmed by 5000iu/daily and it will achieve it's purpose this is a more responsible amount to suggest.

You have to bear in mind that a naked body exposed to sunlight will make 10,000iu ~20,000iu fairly quickly. No one would suggest that our DNA is trying to kill us by producing that amount of D3. The skin only produces that amount because it senses that deficiency status. Once status rises it slows down production.

It really is about time people got their priorities right on this matter.
Absolutely zero adverse events have been recorded under 150ng and the amounts suggested here won't get anyone over 100ng so there is still a huge safety margin.

The danger area is below 50ng and the consequences of that are far far more serious.