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Fight fatty liver disease with bubble wrap
Lipid droplets are round and triglycerides are M-shaped…….
It’s a case of putting, “square” pegs in “round” holes.
It’s a packaging NIGHTMARE.
This is the nightmare, liver cells must content with 24/7.
You see, liver cells are ALWAYS moving fats around. As the supply chain manager, of the body, assembling, manufacturing and distributing resources, is what liver’s do.
And as the most compact energy rich fuel source, moving fats, is a big part of their day.
High energy molecules, are by their very nature, highly combustible.
Dynamite comes in small packages
You can think of free fatty acids, as sticks of dynamite.
They’re a long string of carbon and hydrogens, joined together by high energy, covalent bonds. Since the energy is IN THE BOND, extracting the energy, requires the bond to be broken. This happens during oxidative phosphorylation. The reaction takes place in a special furnace, the mitochondria, and is a CAREFULLY controlled.
It’s a high risk operation.
With teams of molecules, working hard to control, the release of energy.
Inevitably, some of the zing, escapes. When the overflow is excessive, the situation is described as OXIDATIVE STRESS.
Dynamite MUST be properly stored
Now, you don’t leave dynamite hanging around…
If it goes off, in an uncontrolled manner, the consequences WILL BE, devastating.
So, cells work hard, to store their fatty acids, SAFELY, to avoid, lipotoxicity.
Safely storing fat
Now when you’re storing potentially dangerous goods – you cannot just store it in ANYTHING. The fats are stored in special organelles, called lipid droplets.
There are multiple safety protocols put in place.
First off, the three fatty acids are fused to a glycerol molecule, to neutralize the reactivity, forming M-shaped molecules, referred to as triglycerides.
These M-shaped molecules are piled up, together and then wrapped, in bubble wrap.
The bubble wrap is made of phospholipids. Embedded in this bubble wrap, is a collection of enzymes, transporters and signal proteins, which move the fats in and out, efficiently and safely.
Lipid droplet assembly
There are quite a few varieties of phospholipids……
They consist of 2 fatty acid chains, a phosphate group and a head.
It’s the heads, that create the “bubble wrap”.
The ones that matter, when it comes to lipid droplets, are phosphatidylcholine (PC) and phosphatidylethanoamine (PE). They have slightly different shapes – and this matters.
PE is conical in shape, while PC, is cylindrical.
To wrap fats safely
The exact details, of how lipid droplets are formed, is still a little fuzzy, but what is known, is the process happened in the endoplasmic reticulum. Tiny lipid droplets, barely visible, even under an electron microscope, pop off the endoplasmic reticulum….
They consist of a conglomeration of triglycerides, surrounded by a single phospholipid layer.
When the jolly and round, PC phospholipids predominate, in the membrane, the process of making lipid droplets, is EASY and effortless. The fat comes in, the membrane is pinched and filled. Pinched and filled….
They’re just so PC
The affable nature, of phosphatidylcholine phospholipids, means they love forming a scrum, the drops of fat, are easily caught up and enveloped, making lipid droplet assembly, seamless.
The haughty nature of PE, puts a spoke in the wheel.
So it’s a lot harder to pinch off a lipid droplet. A LOT HARDER.
When PC is thin on the ground
Unfortunately, when PC is in short supply, rather than deal with disobliging PE, liver cell, skip the pinching off, of new lipid droplets…..
Opting to fill the lipid droplets, they’ve already go.
The trouble is, the lipid droplets get bigger and bigger.
So does the size of the lipid droplet matter ?
Too big for their britches
Yes. And this is one of those times, BIG is NOT BETTER. The problem with extremely BIG lipid droplets, is they are harder to handle.
- The fat breaking enzymes, struggle.
- The cell’s clean up crew, find disposing of giant lipid droplets a NIGHTMARE – so they don’t do it.
- Likewise, moving GIANT sized lipid droplets around, is significantly more taxing.
The end result……..
Giant lipid droplets dominate
These lipid droplets become visible……… leading to a diagnosis of fatty liver disease. And from the liver’s perspective, all sorts of trouble.
Cells are so full of these giant lipid droplets, they find it difficult to do their job.
- Sugars can’t be stored (leading to hyperglycemia).
- Insulin cannot be cleared (contributing to hyperinsulinemia).
- Lipid metabolism is severely disrupted (think high “cholesterol”)
Basically all hell breaks loose….
So what determines how much PC is available ?
Well phosphtidylcholine is made from choline.
And choline is something, you make.
How much choline is made, depends on genetics, and hormones ! The more estrogen you have, the more choline you MAKE.
Some people come, with a genetic disadvantage, but no worries…….
Choline is found in the diet, particularly in animal based products. The two biggest sources of dietary choline are liver and egg yolks. Of course, if you’re NOT eating these, because you’re following, NUTRITIONAL GUIDELINES… it can be quite challenging, to get ENOUGH.
The under consumed essential nutrient
This is a nutrient that is not on a lot of people’s radar and ironically, it is one that “the powers that be” are increasingly taking aim at.
You see, choline can be metabolized to trimethylamine (TMA), in the gut.
Liver’s then pop an oxygen on to TMA.
And high TMAO levels go hand in hand with BAD BODY CHEMISTRY.
A bad reputation
Now, the evidence that TMAO actually causes BAD BODY CHEMISTRY, is thin on the ground……..
But, when all is said and done, you don’t want high TMAO levels.
Like “high” cholesterol, high TMAO, puts you in the category of a heart attack waiting to happen.
So putting two and two together………
Eating less choline WILL “fix” the problem. RIGHT ! WRONG ! Biology is never that simple.
The unappreciated essential nutrient
Choline is a resource you need, to move lipids around the body, safely………
If your supplies are low, fat metabolism will be adversely impacted.
So, cut your liver some slack…. make sure you stock up on bubble wrap !
Hepatic lipid droplet homeostasis and fatty liver disease. Seminars in Cell & Developmental Biology, 19 May 2020,Fabian Seebacher, Anja Zeigerer, Nora Kory, Natalie Krahmer.
Phosphatidylcholine Synthesis for Lipid Droplet Expansion Is Mediated by Localized Activation of CTP:Phosphocholine Cytidylyltransferase. Cell Metabolism (2011) 14 (4) : 504-515. Natalie Krahmer, Yi Guo, Florian Wilfling, Maximiliane Hilger, Susanne Lingrell, Klaus Heger, Heather W. Newman, Marc Schmidt-Supprian, Dennis E. Vance, Matthias Mann et al
The critical role of phosphatidylcholine and phosphatidylethanolamine metabolism in health and disease. Biochim Biophys Acta Biomembr (2017) 1859(9 Pt B):1558-1572. Jelske N. van der Veen , John P. Kennelly, SereanaWan, Jean E. Vance, Dennis E. Vance, René L. Jacobs.
One of the reasons your belly is protruding ,is your liver is holding onto more fat, than is ideal and that fat, is cramping your liver’s style and putting you at risk of liver failure
Fat can be burned or distributed & stored – where it ends up, depends on which train track, the lipid droplet is loaded onto to……..turns out, the hoghead can be bribed
TMAO acts as a piezolyte, that means, it helps to protect the fish’s proteins, from being “crushed” by the water pressure