A Paradigm of Fatty Acids

Everybody is caught up in the aesthetics

Fat metabolism is complex once you venture past the idea of fat merely being energy substrate. I don’t want to disrespect carbohydrate nor protein metabolism in vivo, but fatty acids are to those two like graduate studies are to junior high.

Carbohydrate metabolism is mostly energy substrate, but has a few complex and intriguing reactions involving glycation (the adding of a sugar moiety onto another molecule). I’m not going to try and pretend that I understand it since I really don’t aside from a few notable exceptions (Advanced Glycemic End products, or AGEs, being formed in blood and becoming artherogenic)

Protein metabolism is mostly substrate for either ffpe tissue array repair or gluconeogenesis. It is by far the most wide-reaching system since everything is made up of proteins and amino acids, but the body takes a fatalistic approach to this; it is very hard for one to manipulate protein metabolism. Aside from a few notable exceptions (leucine as a signalling molecule, arginine as a secretagogue) most oral supplementation with individual dietary amino acids is futile. The best you can do is avoid a deficiency and not major in the minutia.

Now fats; fat metabolism is complex. Many mechanisms of action, many possible fates (of which we really have no control over; take the good with the bad), and intertwined with pretty much everything. Below is a way of viewing fat metabolism that may be of aid to you.

The Four S’s of Fat Metabolism: Substrate, Structural, Storage, or Stimulation

Before I elucidate the 4 S’s, I want to make clear the difference between Triglycerides and Fatty Acids.

Fatty acids are long chains of carbon molecules. They vary in length and also vary in saturation. ‘Saturation’ refers to how many hydrogen molecules are on the fatty acids. For example, below is Stearic acid; a fully saturated fatty acid.

Its just carbon after carbon after carbon (the hydrogens are not pictures; normal nomenclature for this kind of stuff). All fully saturated fatty acids are what we refer to as dietary ‘Saturated Fats’ and are, for the most part, straight lines.

The following is Oleic acid, a monounsaturated fatty acid (Mono = one, in this scenario)

It is unsaturated at a certain carbon, in this case the 9th carbon from the end without the carboxylic acid group (the left). Any unsaturation will cause a kink in the structure and make the fatty acid slightly bendy.

But wait, what about polyunsaturated fatty acids like fish oil? Below is the EPA component, Eicosapentaenoic Acid.

Its about as straight as Gay Pride. It has 6 unsaturated bond areas and thus an incredibly convoluted structure. If you also note the tail end (without the C=O group) the first double bond occurs at the third carbon from the end. This is why this particular fatty acid is called an Omega-3 fatty acid (Omega is often used to denote the end of something, 3 is a 3; the first double bond is the third from the end)

And just to sum things up, a note on ‘Trans’ fatty acids; below is Conjugated Linoleic Acid (CLA).

The bond is a bit different, specifically it is in ‘trans’ formation; hydrogens exist on both sides of the carbon chain at the site of the bond. Notice how the chain is straight-ish despite being unsaturated? (Note: They’re not always straight, but are sometimes)

Anywho, I digress; now for the difference between a Triglyceride and a Fatty acid. The fatty acids are above; they are all carbon chains that vary in length, size, and bendiness. Triglycerides (TGs) are just 2-3 fatty acids bound to a glycerol molecule.

I chose the above picture to illustrate that all three sites for fatty acid bonding does not need to be the same fatty acid. Whatever fatty acid binds to glycerol will be based on whatever fatty acid is physically close to the Fatty-Acid Synthase enzyme when it needs one; its quite an indisciminate process.

Also, Triglycerides don’t need to have 3 fatty acids; sometimes they have two. Below is Phosphatidylserine (PS), a neurological health supplement that is also found in high levels in fatty fish.

You can check https://www.dietagem.com/quitoplan-funciona-emagrece-resenha/ where you will find more info on the best health supplements.

The glycerol is in the middle(ish) of the picture above, and to the left of the picture are the C=O and the R groups. R, in this case, just means ‘insert any fatty acid’. The right side of the structure is a phosphate group (PO4) bound to the amino acid Serine. This is the triglyceride structure that is most commonly found in membrances (along with others like phosphatidylcholine (PC), phosphatidylinositol (PI), spingolipids, cardiolipin, etc.)

A general rule of thumb is that triglycerides are found in the diet, and they are stored in the body; between A and B, the glycerol backbone sometimes breaks off and the free fatty acids go about and do their thing.

And now to elaborate ‘their things’…

 Substrate

The things that comes to mind usually when people think of fats is the ‘burn fat’. This is one of the two main ways in which fats act as substrate. Specifically, they can act as energy substrate (for subsequent ‘burning’, or usage, in the mitochondria to create ATP and provide fuel to the body) or they can act as prostaglandin substrate.

Prostaglandins are potent signalling molecules. Kind of like hormones, but they tend to act locally rather than systemically (stuff like testosterone can be created in the testes and just float to your biceps; prostaglandins will usually stay in or near where they are created). There are numerous prostaglandins (divided into two main classes, eicosanoids and thromboxanes. A rule of thumb is that eicosanoids are made from omega-3 fatty acids and thromboxanes from omega-6 fatty acids)

Structural

Fatty acids can also be structural. This is different from ‘storage’ (to be discussed) as it denotes a purpose. Fatty acids provide structure to cells by being incorporated into a cell membrane. The membrane is made up of phospholipids (which are lipids (fatty acids) bound to phosphate) and the general traits of the fatty acids may contribute to the attributes of the membrane. Its a young field, but highly unsaturated fatty acids may increase membrane fluidity and subsequent transporter protein function and health status; likewise, saturated fats may reduce fluidity.

The significance of fluidity as determined by diet is not known, and the latter point (saturated fats may reduce fluidity) may be redundant as the cholesterol molecule can be incorporated into membranes to increase fluidity (cholesterol and saturated fat are very correlated in the diet)

Storage

This one is fairly straight forward. If fatty acids are in excess and the mechanisms for them to be deposited as triglycerides is active, they can be stored as triglyerides. This is their storage form; mostly in fat cells (adipocytes) and also the liver to a lesser extent, but can be stored in minute amounts anywhere.

Triglycerides are inert, and don’t do too much special stuff in and of themselves. It is, however, a possible fate of dietary fats.

Stimulation

This is the interesting one in my opinion. Fats as ligands and interacting with enzymes.

A ligand is a molecule which can act upon a receptor and induce that receptors effects. For example, testosterone is just a ligand for the androgen receptor; all effects that you associate with testosterone are through the androgen receptor being activated by a ligand.

Some fatty acids may be ligands. Specifically fish oil (EPA and DHA) may influence the PPAR system of nuclear receptors and confer benefits to fat metabolism and heart disease. Interactions have also been noted with GPR120 via this mechanism.

In regards to enzyme inhibition, some fatty acids can inhibit enzyme function. Oleic acid (olive oil), Myristic acid (Dairy) and Lauric Acid (Coconut Oil) can all inhibit isoforms of 5-alpha reductase, the enzyme that converts testosterone to Dihydrotestosterone (DHT). So for those of you who are genetically susceptible to hair loss and want to have a hair growth improvement, take note.

Why do I write this?

Fatty acid metabolism is complex, and it is significant. I do not know enough about prostaglandin metabolism to come to even preliminary conclusions on it, but the last two sections (storage and stimulation) cause an interesting synergism.

The fatty acids you eat are the fatty acids stored in your fat tissue. If you eat fish oil, you store fish oils. If you eat CLA, you store CLA. You are what you eat in this regard. In addition, there is always a rate of fatty acid turnover (Note: Linked citation is not 100% accurate, but I was at a loss as to what to link; attached is a free full text of adipocyte regulation that should suffice).

Fatty acid turnover + customization of stored triglycerides through diet == Theoretical ligand interactions happening 24/7. This is not proven, (Hell; I have no idea what kind of experimental model would validate this in vivo) but it is theoretical. A triglyceride gets disassociated via Hormone Sensitive Lipase (HSL) and just floats around, and has the potential to act against target molecules until it is used for substrate or otherwise re-esterified as a triglyceride to act in the future.

The above is actually the main mechanism of action of TTA (Tetradecyl Thioacetic Acid), a thia fatty acid that cannot be beta-oxidized for energy. It induces thermogenesis (heat production) via acting on the PPAR system, and then goes into hibernation via being stored as a triglyceride. Eventually it gets released again, and theoretically can act again (I say theoretically as I have seen no data on it directly, but pharmacokinetic data (how long it stays in the body) varies widely, indicative it is being stored at random).

So in sum, fatty acid metabolism is complex as hell but important as hell. Hopefully the 4 S’s can help direct study on the topic and give a paradigm conducive to learning.

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Comments

  1. cdc_th says:

    ” R, in this case, just means ‘insert any fatty acid’. ”

    If I may be pedantic, the R in this case of course doesn’t refer to an entire fatty acid, as the carboxyls of such are depicted separately. Instead, it refers only to the carbon chain/tail of the fatty acid – as I’m sure you know.

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