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According to Wikipedia,

"Palmitic acid is the most common saturated fatty acid found in animals, plants and microorganisms. It is also the first fatty acid produced during fatty acid synthesis and is the precursor to longer fatty acids. As a consequence, palmitic acid is a major body component of animals. In humans, one analysis found it to make up 21–30% (molar) of human depot fat, and it is a major, but highly variable, lipid component of human breast milk." (https://en.wikipedia.org/wiki/Palmitic_acid)

Yet, specifically palmitic acid is also said to be "harmful" (that it increases LDL levels and puts people at risk for heart disease), per the World Health Organization (http://www.freezepage.com/1348239076FHWAJDADVT).

So, I am skeptical --- possibly most ubiquitous saturated fatty acid in nature and a central component of our fatty acid metabolism, is somehow "more" dangerous/unhealthy compared to other saturated (or unsaturated) fatty acids? I'd suspect the opposite should be true -- it seems to me it should be the saturated fatty acid we should be most capable of handling well!

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Let's first clarify some concepts. Free fatty acids, including palmitic acid, are not present in animal tissues (or in the diet) to any large extent; they are esterified with glycerol to from triglycerides (fat), which is the storage form. This is a very important distinction, because triglycerides are chemically inert molecules that can be stored in very large amounts in cells without causing problems (adipocytes are pretty much just one big fat droplet), while free fatty acids are dangerous to organisms because they disrupt cell membranes --- fatty acids are basically soap.

When nutrition studies like the WHO report talk about dietary intake of "palmitic acid", they really mean intake of triglycerides that contain a large proportion of esterified palmitic acid as side chains. There is a large body of epidemiological studies indicating that intake of fats rich in palmitic acid correlates with cardiovascular disease and other "metabolic" disorders, although some reports show no significant effect. In clinical trials, replacing saturated with unsaturated fat seems to provide some health benefit; but there also are studies indicating that monounsaturated fat can be worse than saturated fat. So there is some evidence that too much saturated fat is problematic, although the issue is not straightforward.

The causal mechanism is to my knowledge still not clear. You are right that cells are normally perfectly capable of handling palmitic acid; it is a good substrate for beta-oxidation and a common fuel source for human cells. However, in pathological situations, free fatty acids can accumulate in cells and in the blood, probably because of excessive lipolysis. Many studies show that this can cause insulin resistance and trigger inflammatory signals, and even cell death by apoptosis. Some reports show that palmitic acid in particular causes these effects, whereas oleic acid (monounsaturated) does not, but I don't think there's any consensus on why palmitic acid is special.

My own hypothesis (if I may be so bold :) is that palmitate only appears to be special because cells have evolved to sense it as a "proxy" signal for free fatty acids in general. Since fatty acids are clearly dangerous to cells, sensing them is important, and because palmitate is the naturally most abundant fatty acid, it would be the easiest fatty acid to detect. It is known that palmitate is recognized by toll-like receptors, in particular TLR2 and TLR4, and that sensing by these receptors trigger "proinflammatory" signalling. But this alone doesn't prove my "proxy" hypothesis, of course.

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    $\begingroup$ Nice answer, +1! Can you add some resources which make you think "palmitate only appears to be special because cells have evolved to sense it as a "proxy" signal for free fatty acids in general"? I mean, at least a verified basis for a hypothesis is better :) $\endgroup$ – another 'Homo sapien' Mar 1 '17 at 13:19
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    $\begingroup$ Sorry, I don't really have any reference for that last paragraph --- it's just a hypothesis, purely based on reasoning from principles. It is clear that palmitate does causes signalling responses (it's known to be sensed by TLR4), but I know of no clear rationale why palmitate would be physically more dangerous than other long chain fatty acid. This leads to my "proxy" hypothesis. As I said, it's just a hypothesis, I have no proof. (I actually hesitated to put this part in, as it is pure speculation, but I thought it could be interesting to share.) $\endgroup$ – Roland Mar 1 '17 at 13:34
  • $\begingroup$ @another'Homosapien' Done, but that is not really the key part of the argument ... $\endgroup$ – Roland Mar 1 '17 at 14:16
  • $\begingroup$ +1. Only one thing to say - no one will disallow you to be bold; men often do that. Being too bald, however, may be arguable in science ;-) $\endgroup$ – AliceD Mar 1 '17 at 14:36
  • $\begingroup$ +1 great answer indeed : ) I'm aware that fats are both generally consumed (eaten) and stored as triglycerides, not as free fatty acids (though i did not explicitly state that in my question, since i thought that was obvious/well-known). But, I was not sure why nutritional research seems to specifically single out (triglycerides with) palmitate chains with such criticism/disdain (especially for such a common and centrally important fatty acid). $\endgroup$ – ManRow Mar 2 '17 at 12:04

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