G'day, my name is Dr. Oreck Bishop and welcome to my podcast and videocast station. As always, I really do appreciate you stopping in to have a listen. Look, today I want to talk about something just to make sure we get our heads around how lipids move in the body and I guess what I want to try and articulate is that when we think about lipids and lipoprotein particles moving around the body, the main role of those lipoprotein particles is actually to deliver an energy source. So I've simplified that. Have a little look here. If we think about energy, then the gut will absorb fats. which get bundled up into chylomicrons and get into the bloodstream by the lymph circulation. Those fats then get exposed to the tissues and the tissues have an enzyme called lipoprotein lipase. Now, lipoprotein lipase acts on the chylomicron. and gets out the triglycerides for those tissues, whether it's fat tissue, muscle tissue, or whatever. Then when that chylomicron has had the triglycerides taken out, it becomes less dense because, sorry, it becomes more dense because the triglycerides occupy a lot of space and we end up with denser particles. One is an intermediate density lipoprotein. And one is a low-density lipoprotein. Now, these lipoproteins are remnants of that process. They're not the bits that the body actually wants. They're remnants. Now, you remember LDL cholesterol, that's central to our issues with coronary artery disease. So interestingly, it's a remnant that's potentially kicking around that gives rise to the issues that we have when it comes to cholesterol in the wrong place. So what does the liver do? The liver doesn't produce LDL cholesterol. The liver produces a particle again for energy, which is called a very low density lipoprotein. Now a very low density lipoprotein looks an awful lot like a chylomicron. And what's its job? Well, basically to go to the tissues where it gets acted on by lipoprotein lipase to split out the triglycerides, get the energy. And then it leaves these remnants in the bloodstream, which then get taken up by the liver, which begs the question, why do we have cholesterol in the chylomicron and the very low density lipoprotein? Well, the body does need cholesterol and we do absorb it and it does make up the particle. And every tissue in the body actually has LDL receptors. So it can take up that LDL. and use it for synthesis. And whatever that synthesis is, it might be repair, it might be formation of a hormone. So really, really interesting. So let's look at that in a slightly different way. And what I'm going to do is share screens so you can see this in a different image. And here we go. Here. is dietary fat comes in through the gut, the intestinal epithelial cells, gets absorbed and turned into a chylomicron, which floats through the lymph system, ends up going through the body and giving rise to free fatty acids, leaving remnants. Remember, the liver doesn't make remnants. The liver makes VLDL. which is a lot like a chylomicron, does exactly the same, gets affected, acted on by lipoprotein lipase, giving up its products to the tissues that need it. But lipoprotein lipase, by taking away the triglycerides, leaves us with a lipoprotein, a little vesicle that's got more cholesterol in it and more and more cholesterol and less and less triglycerides leaves us with a LDL particle, a low-density lipoprotein particle, low-density lipoprotein particle and cis particle that we believe is the one that ends up in the lining or the intima of the blood vessels. So when we think about all that, what's happening in the liver when we're giving a statin? Well, the liver is able, like every other cell in the body, to produce cholesterol. Probably doesn't need to produce very much because there's lots cycling and it can just take it out of the system. But here's how the statins, which block the acetyl-CoA, HMG-CoA reductase pathway, work. Bembedoic acid, actually, which is an agent, very similar in its function to statins, works in the same way. So follow me here. Acetol-CoA becomes HMG-CoA reductase. HMG-CoA reductase gives rise to mevalinate. Now, if we can block HMG-CoA reductase, we don't produce mevalinate in the cell. And mevalinate is central to production of cholesterol. Now, if the cell is not producing cholesterol, Then it has internal regulatory mechanisms, which says, well, we need to be in a position to potentially make or utilize more cholesterol. So it looks to absorb that cholesterol from the bloodstream. So as we turn off the production of cholesterol within the cell, within the liver cell, in fact, but every other cell in the body, remember, those cells respond by putting more receptors for LDL cholesterol. on the cell surface so that they then take more from the circulation. Well, I hope that makes sense. It's a way to reframe the way we think of LDL cholesterol. It's not the primary thing that the liver produces. The chylomicron is what the energy supply is from the gut for fats going to the tissue. Very low density lipoprotein is what the liver produces to go to the tissues as an energy source. Those remnants are flying around the body. The liver doesn't make LDL cholesterol, but the liver uptakes LDL cholesterol and it uptakes more if we reduce the production of cholesterol within each cell. It's really important. to understand that interplay. And the other thing that's really important to understand is that the measured cholesterol in the bloodstream, so when we take a blood test and you get that checked and your doctor evaluates it, and we look at LDL cholesterol, that cholesterol is the measurement of LDL particle cholesterol within the bloodstream. That is not. the amount of cholesterol in each and every single cell. They are two separate things. There's the circulation where all these little particles pass by, and then there's every cell in the body, which has the ability to either take LDL cholesterol from the bloodstream or make cholesterol itself via its own metabolic pathways. Well, I reckon that's pretty interesting. I hope you find that. interesting as well. It gives us a little bit of clarity as to where those lipoprotein particles fit in and what they're doing as they move around the body. But think of it in terms of energy, and that's what our main driver is, getting that triglyceride around the body is an energy fuel source, and the other is repair and synthesis and each and every cell. can uptake cholesterol from the bloodstream for that. Well, I hope that makes a bit of sense. For now, I'm going to say goodbye. If you've got any queries or questions, drop us a note. I do love your questions. In fact, I had a question from someone the other day. I'll see if I can find it quickly. It was from Colin, and he wanted to know about what are my thoughts on AV ablation. So AV ablation is when you... ablate the node between the atria and the ventricles that node is if you like a capacitor between the top and the bottom stopping too many electrical signals getting through from the top to the bottom which is protecting the ventricle if the top chambers were to go into atrial fibrillation so it's a really important node it allows the delay between the top and the bottom When we ablate it, we normally replace that with a dual chamber pacemaker so that we can activate the top and the bottom. Sometimes if the person is having AV nodal ablation because of atrial fibrillation and they will never get back into normal rhythm, then there will be an atrial fibrillation. The AV nodal ablation is there to block the transmission of the electrical signal from the top to the bottom. so that the heart rate can slow down and be controlled and reduce symptoms. What do I think about AV natal ablation? Well, for those people who need it, it's essential and it's really important. Ideally, we want to work around it if we possibly can, and hopefully not in the situation where it's required, but it is one of the treatment options for rate control for atrial fibrillation when really very little else will. Very little else has worked. So that's for Colin. If anyone else has any queries or questions, drop me a note. For now, I am going to wish you the very best. I hope you live as well as possible for as long as possible. Take care and bye for now.
