Exploring the link between the liver, lipids, and thyroid hormones.
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We’re back for another edition of Thyroid Thursday, and I got a lot of requests to do a video on the liver, lipids, and thyroid hormones. There’s a lot to cover, so buckle up. It’s gonna be a bumpy ride.
So we need to get these lipids to the liver, and then we need to do something with them. We’re typically talking about free fatty acids, and free fatty acids are typically packed together as something called “triglycerides.” And the other lipid we pretty much talk about is cholesterol.
So we get a percentage of these things coming into the liver, and then the liver’s gotta do something with them. So where do these things come from? Well, free fatty acids, they can come from our diet. So as we eat food, those fatty acids are broken down, and absorbed, and then they get into the body and then they head to the liver where we do something with them.
Fatty acids can come to the liver from the adipose tissue. So when the adipose tissue gets signals to release triglycerides, it can release them into the bloodstream. Those triglycerides can go to the liver where we can use those triglycerides many times as energy.
And then we can have de novo synthesis of fatty acids, and that means that the liver can actually generate fatty acids. And I’ll explain why they would do that in a little bit.
As far as cholesterol, where does that come from? Well, we can get some from our diet. We can also get some from the other cells in the body that have generated cholesterol and they need to get rid of it. And they’re typically packed up into these HDL molecules and come back to the liver. And that’s why people say HDL is “good cholesterol,” because it’s going back to the liver. Yet, it’s not good or bad.
Cholesterol can also be made. De novo means the liver can generate its own cholesterol. And we’ll talk about how that happens as well.
So the exit strategy for these things… We use free fatty acids to make energy. We call that beta-oxidation. And that’s really what a lot of people are trying to do when they’re on a high fat, low carb diet, is use fats as a fuel. If we don’t need those free fatty acids for beta-oxidation, then we can pack them up back into triglycerides and we can store them in the liver in these things called lipid droplets. So that way later on when the liver needs some free fatty acids for energy, they’re right there and available.
If we don’t need those free fatty acids that were packed back up into triglycerides, they get clumped into another lipoprotein, VLDL, and VLDL can go out into circulation.
Well, now that we’ve got cholesterol in the liver, either from our diet, from the other cells, or made de novo, then if we don’t need to make energy from it, those triglycerides become VLDL and go out into circulation to support other tissues or get stored.
We can use that cholesterol to support the cell membrane, make healthy plasma membranes for the hepatocytes — that would be a good thing. We could use that cholesterol to make bile acids, the things that help break down your fats, help kill the bacteria in your gut, help maintain the tight junctions. Really important.
Or we could just say we’re going to just get rid of them. We’re just gonna push that cholesterol into the bile and get rid of it.
Now, what role does thyroid hormone play in all of these steps? Well, to get these chylomicrons and LDL and HDL to dump their contents into the GI tract or the liver, we need receptors for these things to bind to and get into the liver cells. These LDL receptors are controlled by, guess what, T3. So T3 upregulates those receptors.
So if we have a low T3 state, those receptors don’t work so well. Matter of fact, there’s an enzyme that’ll just degrade those LDL receptors. So low T3 state in the liver = LDL cholesterol piles up. We may even see an elevated HDL number, too.
Number two, to get those triglycerides from your adipose tissue into the liver, you need more transport proteins. And guess what regulates those? T3. You got it. So if you have a low T3 state at the liver, you’re gonna have triglycerides piling up in the bloodstream.
Number three, we talked about de novo synthesis. So when there’s a low T3 state inside the cell, inside the liver cells, your mitochondria don’t work as efficiently, and they can’t burn as much glucose. So then what happens is the glucose that was converted into something called acetyl-COA and went into this thing called Krebs Cycle that you learned about in seventh-grade science class, the glucose can’t go through the cycle to go through the electron transport chain and make the “P” that you want for energy. Instead, it gets pushed back out of the Krebs Cycle.
And then one of two things can happen to it: It can either be converted into more free fatty acids, or it can be converted into cholesterol. And guess what you need to convert that citrate into HMG-CoA, which is the main enzyme that converts and produces cholesterol? You need T three.
Okay, so next… We talked about fatty acids. We can burn those to make energy called beta-oxidation. But what do you need to regulate beta oxidation? You need T3. There’s an enzyme, CCPT1, that helps transport the free fatty acids into the inner mitochondrial membrane. It’s also regulated by T3. So if you have a low T3 state, you may not be able to burn fatty acids.
So if you’re going on a low-carb, high-fat diet and you’re like, “Hey, I don’t feel good. I don’t have energy, I’m not losing weight…” it’s because you have a low T3 state and you’re unable to burn those fats!
Number six. If I have extra fatty acids and can’t burn them in beta-oxidation, I can store them in these lipid droplets. When we want to use the free fatty acids in those lipid droplets, we need an enzyme to kind of hydrolyze and release the free fatty acids. Guess what it needs? T3. So if you have low T three inside the cell, you can’t break down the lipid droplets and it’s gonna lead to something along the lines of fatty liver disease.
Now we’ve got number seven. I wanna make bile acids. But guess what you need? T3 regulates the primary one of the primary bile acid genes, CYP7A1. That’s the rate-limiting enzyme to make bile acids. So if you have a low T3 state, you can’t make sufficient bile acids.
Number eight, if I just want to get rid of the cholesterol, I can push it through this transport molecule, ABCG5 receptor, and push it right into the bile. But guess what it requires? T3.
Alright, and then we talked about T3. If you have a low T3 state, this enzyme PCSK9 actually degrades the LDL receptor. And now I can’t get those fatty acids and cholesterol into the liver, and they stack up in the bloodstream.
So what are the signs of low T3 in the liver?
First: a low T3 or free T3 in the blood. If it’s low, it’s probably a good indication that we’re going to have some problems in the liver.
Number 2: a low free T3 to free T4 ratio. What this means is that you might have plenty of T4, but you’re not converting it well to T3. You could even have normal free T3 and normal free T, but if the ratio is low, you’re probably not doing a great job converting that T4 to T3 efficiently.
You could have high cholesterol and LDL in your lab work. You could have low bile production, which means you’re gonna have problems with breaking down fats and digestion. That may also lead to bacterial overgrowth and leaky gut and food sensitivities.
You can have high triglycerides and VLDL. You can have decreased insulin production or loss of your first-phase insulin response due to changes in bile acid concentration. You can have glucose or insulin resistance, meaning both of those could be high. You can have high ferritin and you can have high or low CRP.