Welcome to Dr. Warrick's podcast channel. Warrick is a practicing cardiologist and author with a passion for improving care by helping patients understand their heart health through education. Warrick believes educated patients get the best health care. Discover and understand the latest approaches and technology in heart care and how this might apply to you or someone you love. Hi, my name is Dr. Warrick Bishop and I'd like to welcome you to my podcast and videocast station and of course I'd like to welcome you to the Healthy Heart Network. Today I'm going to be talking about how we move fats around in the body, how lipids move around in the body and I hope you've had the chance to listen to a previous podcast where I defined hydrocarbons, fats, oils and... Because this really follows on from that. Very quick recap. A hydrocarbon is something that's made up of hydrogen and carbon. It's pretty straightforward. If we take a chain of them, say a chain of 16, 18 or 20, because these are the sort of changes that occur in our body. If we tack an oxygen atom and an oxygen and hydrogen together to the end carbon atom, we create a free fatty acid. If we take a whole heap of those free fatty acids and put them in with a group of carbon atoms which are linked together in groups of threes, and each of those groups of threes have an oxygen and hydrogen compound attached, then those free fatty acids can interact with that group of three, joined together through that backbone structure, if you like. And that gives us what's called a triglyceride. And that's the way the body tends to transport and store free fatty acids, which then become triglycerides, or therefore transport and store fats within the body. Remember, cholesterol is a hydrocarbon. base in a ring form so there's several rings all put together there's a hydrogen and oxygen together hanging off one of those rings and that makes it a steroid alcohol don't need to remember that but that has a little bit of water solubility in the body though the OH the oxygen and hydrogen component can act as a point where fatty acids can join up to cholesterol so now We've got a joint structure of a few rings, looking like the basis of cholesterol, plus a chain of free fatty acids. So the rings and the chains are joined together. That's called a cholesterol ester. And the bulk of cholesterol in the body is in that form. That is for storage and for usage. But a cholesterol ester is not water-soluble at all. It's very... very hydrophobic. Hydro, relating to water, phobic, scared. So it repels water. Same as the triglycerides. So as we move these complex lipids around the body, we need a mechanism to do it. Remember when we talked about the backbone of three carbon atoms which form the basis of triglycerides, if instead of putting three fatty acids in a row on those three available carbons. If we replace one of those fatty acid chains with a phosphate group, we create a phospholipid, a combination of phosphate and fat. Phospholipid. The important thing about phospholipids is that the phosphate bit is able to interact with water. It is hydrophilic. Hydro, meaning related to water, philic. meaning it attracts or loves. So we've got our triglyceride, hydrophobic, scared of water, our cholesterolester, hydrophobic, scared of water, and we've got our phospholipid, which is hydrophilic. Now, with that quick backdrop and a reminder of where we got to, Today, I'm going to move on to the next bit, which is how we then move these lipids around the body. And the concept that I want to bring into play are the being of special proteins which relate to lipids. So these are very special proteins that can interact and bind lipids. Proteins, I want you to think of them as sort of fairly strong and dense. Lipids as sort of floaty and, if you like, not so dense. Proteins can be water soluble and interact well with water. And the particular proteins that we talk about are things called apolipoproteins. Don't need to remember that, but the term apoprotein will come up. Apoprotein is a shortening of apolipoprotein. These apoproteins are both hydrophobic and hydrophilic. And that means that they've got two components, almost in a twisted or helical arrangement. The amazing thing about that is it means that they can twist any one component, literally hold these hydrophobic... or water-repelling lipids within their structure and other components, they can literally interact with water or serum and therefore move around the body. Quite amazing, these apoproteins. And there's a few different types of them. So we're going to talk about them a little more as we progress. But what I'd like you to do is to imagine we've got... A number of components which are going to become the surface or capsule of our little balls or spheres that are going to carry our fatty payloads around the body. Well, I've mentioned apoproteins. They are water-soluble, so we're going to put their component on the outside of this shell structure. I mentioned cholesterol. Cholesterol before esterification has the... OH or hydroxyl group attached, and therefore that can interact with water a bit as well. And so we have hapoproteins, cholesterol, and remember I also mentioned phospholipids, which have a water-soluble head and a water-insoluble tail. Well, imagine now we can make a spherical crust out of our apoprotein. out of our cholesterol before it's esterified, our steroid alcohol, and our phospholipid. We've now got this core, sorry, we've now got this sphere where the capsule around the outside, the surface, represents externally hydrophilic or water interacting. moities or structures but all pointing to the inside are hydrophobic or non-water reacting areas and so that center that pouch that we've created now becomes the place where we can put in our triglycerides and put in our cholesterol esters and so now we've got this amazing little particle this round sphere where the outside crust if you like, is protein, our apoprotein. It's phospholipid, so it's got some water interaction available and a tail that doesn't water interact and a bit of cholesterol. We've also got a central core where all our fat can sit. And so now you can imagine that core where it's like the crust of the earth. It's a bit sort of thick and dense at the top and in the middle, sort of molten fatty soft stuff. The density of that entire sphere is really driven to a large degree by the proteins in the surface capsule because the proteins are closely knit together in the terms of the way they're made, whereas the fats, the complex lipids, they're quite spaced out and therefore not very dense. In amongst that array of hydrocarbons and fats, We also, within these particles, carry some fat-soluble antioxidants and fat-soluble vitamins. Well, a good example of both of those is vitamin E. Vitamin E tends to have a role in modifying oxidation and mopping up oxidation byproducts, therefore an antioxidant. And vitamin E is also one of the vitamins that's fat-soluble that moves around the body together with vitamin A, D, and K. So all the fat-soluble vitamins, basically A, D, E, and K. They're also going to be, because they've been dissolved into some of those fatty particles, part of these transport spheres that are going to move around the body that we're going to talk about. So, we've got an outer layer, which I've told you about, and an inner core, where all the fatty stuff is going to sit. I'm going to introduce some extra terminology. The apoprotein, which is going to be part of that sphere, is really important because that apoprotein not only holds the complex fats inside our sphere, but that apoprotein presents to the surface a particular key, if you like, or a particular structure, binding receptor, an area that allows it to then react with other binding receptors or areas. So there's a lock and key almost occurring where our apoprotein designates where our sphere can land, what its target is based on the receptor of the target. So we've got receptors in the tissues that receive these particular apoprotein shapes or forms. I'll touch on that a little bit more in a moment. Now that we've got all these apoproteins in a sphere, and we've got some cholesterol in there, and we've got some phospholipid in there, plus we've got that fatty central core of triglycerides and cholesterolester, we've now got a particle. And that particle is full of lipid and protein. And I don't know if you guessed it, but that... particle is now called a lipro, referring to lipid, protein, a lipoprotein. So now we're going to move on to talking about lipoproteins, which are really these particles with the external sphere, protein-driven, and the internal core, mainly the fat carrying component. Lipoproteins, these spherical structures, they are moving through the bloodstream and delivering fatty acids, triglycerides and cholesterol acids to where they're needed. Now, as the core of these spheres, as the core of these... lipoprotein particles is removed then the density of that lipoprotein particle increases. If you think about that nice and slowly the protein shell remains the most dense bit of the particle. The fatty core is the least dense bit. So as we take out more and more of the fatty core as this particle travels through the body and this fat, this lipid, is sucked out of the middle of these particles, then the particle gets smaller and smaller without necessarily the sphere components being reduced. And so as the particle gets smaller and smaller, the surface proteins pack in tighter and tighter, and lo and behold, As the particle goes from bigger to smaller, it goes from a lower density to a higher density. And so as we talk about these lipoprotein particles, you will hear us talk about their densities. We'll talk about low density or high density or even very low density. So that's to do with the core fatty components being taken out. while the surface components, which really hold the bulk of the structure, remain intact and shut down or close down on themselves, increasing the density of that particle. I hope I didn't go too fast there. So let's start with the largest particles, and the largest particles, of course, are going to be from where... Either the fat is absorbed into the body or produced in the body and needs to be sent away. So we have particles that are made in the gut. The particles that are made in the gut are from the absorption of fat. And as that's all pulled together, we create large particles called chylomicrons. chylomicrons. You don't have to remember that, but I'm going to give you some extra interesting facts about them in just a second. So chylomicrons are the fatty particles from the gut. Well, the liver can create fatty particles as well. And so if the liver creates fatty particles with triglyceride and cholesterol in them, then the particle that the liver creates is the beginning particle is a very. low-density lipoprotein. So it's a very low-density, which means it's a great big fat thing with a thin crust and lots of cholesterol and cholesterolester and triglyceride stuffed in the middle, lipoprotein. VLDL is the abbreviation we often use. So from the gut, chylomicrum, from the liver, a very low density lipoprotein, and these are either the absorption or production distribution transport particles. Just to give you some idea for what it's worth, the chylomicron is massive in comparison to the other transport particles in the bloodstream. So the chylomicron has a diameter of about 500 nanometers. Again, you don't need to remember that, but to put it into context, the diameter of a very low-density lipoprotein is about 50 nanometers. So that's a tenfold difference. Now, if we think about spheres, then volume is related to radius cubed. So the radius is 10 times different, therefore 10 times different cubed. is a thousand times difference in volume, which is pretty insane actually. So that's a huge variance. And I don't think it's going to bother us too much, but I thought it was such a fascinating fact, I thought I'd tell you. So our lipoproteins, our great big lipoproteins, the hugest one being the chylomicron and our VLDL, very low density lipoprotein, set off from the gut or from the liver. and start to move around the body to where they need to give up their triglyceride or cholesterolester to the tissues for energy consumption or for storage. As they do that, then there's a removal of the fatty centre and the particle density starts to reduce. So... As that happens, or for that to happen, there's a couple of things that need to come together. The first is that that particle, the lipoprotein particle, whether it's the chylomicron or the VLDL, needs to have an apoprotein on it, which is its signature or marker, which then needs to match up with the tissue it's going to go to. But the other thing is... For these large particles, chylomicrons and VLDL, to give up the contents of their sphere, of their lipoprotein, they need help with a special enzyme. And an enzyme is just something that facilitates a process to occur. So there are fantastic helping chemicals, fantastic enzymes, fantastic facilitators the fatty core of chylomicrons and VLDLs to be extracted within the capillaries and move into tissues. And so the enzyme, which you don't need to remember the name of for that, is lipoprotein lipase. Lipoprotein, obviously, relating to what the particles are called. They're all lipoproteins, lipid and protein particles. And lipase just means dissolves fat. or breaks fat down so it's a a enzyme that breaks down fat within lipoproteins which are the fat and protein spheres that we're talking about nothing confusing about it but it's terminology that is easy to lose if you're not using it regularly i'm just mentioning it so that you understand where some of these terms may fit in and it just fills in the gaps and helps bring some detail to the discussion Remember I said that the apoproteins, these proteins that sit in the surface of the lipid protein of the particle, the apoproteins have their own characteristics which allow them to specifically link to very particular target tissues. Well, I'm going to mention a couple of those because they're going to be fairly important. Apoprotein B48. This is pretty well unique to the chylomicron, but as the chylomicron moves through the body and changes its density and reduces the centre fatty core and becomes more dense, it picks up an apoprotein E, which it also shares with VLDL, or very low density lipoprotein. This apoprotein E, there is a receptor for that on the liver, so this is where these particles can end up after going through the circulation and delivering their payload where they need to. There's an apoprotein B, in fact, specifically apoprotein B100, but let's stick with apoprotein B, and this is going to be an important one. down the line, because apoprotein B is the one that is linked to the low-density lipoprotein receptor. So there is a receptor for LDL. Remember, we've gone cholomocron, least dense, VLDL, very low-density lipoprotein. Next, next dense, there is an intermediate-density lipoprotein. which I haven't talked too much about, but it's an intermediary. And then there's a low-density lipoprotein. And we're going to talk about this a lot as we progress through the series on cholesterol and coronary artery disease and statins and all the stuff around that, because LDL cholesterol is the one that we really think is central to what goes on in coronary arteries. And so ApoB is a very good marker of exactly how much. LDL cholesterol there is in the bloodstream. There's also an apoprotein lowercase a or little a, apoprotein lowercase a. This is an apoprotein of its own that's a bit, well, it's really beyond the scope of this particular discussion. And apoprotein, oh sorry, apoprotein a or apolipoprotein little a is a moiety that sits close to apoprotein B100, and so is very closely linked to the LDL, or low-density lipoprotein receptor or grouping. But lipoprotein little a, or apoprotein little a, is an inheritable chain of protein that seems to hang off the side of the apoprotein B location and causes problems of its own. We're going to talk about apolipoprotein, little a. sometime down the line because it's a very important risk factor in coronary artery disease. So it's an LDL type particle. So where are we? We've got fats. We've talked about moving fats where they're consumed or absorbed and how we then move them around the body. And we've also touched on how we deal with fats that are produced within the body. If we're talking about fats that are ingested and then sent around the body through the intestine, we're talking about the chylomicron. If we're talking about fats that are generated de novo within the liver, then we're talking about very low-density lipoprotein. Both of these large particles travel around the bloodstream, giving up their lipid core, and that's facilitated by that clever enzyme called lipoprotein lipase. We've talked about the different particles and the different densities, and we've also talked about the receptors required on those particles, which is related to the apoprotein, which allows those particles to lock in or target specific organs that have receptors for that particular protein. So our main particles are the chylomicron, A very low-density lipoprotein. There is an intermediate-density lipoprotein. I won't dwell on that. There's a low-density lipoprotein. And you guessed it, there's a high-density lipoprotein as well. Well, the chylomicron is related to the food we consume released from the liver. Sorry, released from the intestine. The food we consume released from the intestine. That's our chylomicron. Our very low-density lipoprotein is related to liver production, and that can really only occur when there's glucose in association with free fatty acids together with cholesterol within the liver, and all that can be packaged up and sent around the body. The low-density lipoprotein comes about as these other lipoprotein particles give up their central core and become increasing. their density so they go from very low density to intermediate density to low density so low density lipoprotein LDL is the one that we tend to be most focused on when we're talking about our risks of coronary artery disease so now you know where that fits in all these guys tend to give up their fatty acid payloads Chylomicron, VLDL, LDL are all predominantly agents for moving a fatty acid payload or a triglyceride or fatty payload around the body and giving that payload up. HDL cholesterol, high density lipoprotein on the other hand, represents our mechanism for bringing cholesterol. or triglycerides back from the periphery toward the centre of the body or back to the liver. High-density lipoprotein is our mechanism for, instead of giving cholesterol away, it is able to potentially take cholesterol up. High-density lipoprotein is characterised by having its apoprotein as a very specific apoprotein called apoprotein A1. There are some variants on that, but apoprotein A1 is the simplest way to think of HDL cholesterol. You probably don't even need to remember that, but there are specific apoproteins, as you might imagine, for HDL cholesterol. So I've told you one role of HDL cholesterol, and that's to bring a fatty acid, a fatty... payload back from the tissues. It can take cholesterol literally out of the arteries from the foam cells and macrophages that may be in there at the locations of plaque formation, for argument's sake. But HDL cholesterol has another role as well. It's the main particle for delivering cholesterol to the adrenal and testes for hormone formation. So HDL cholesterol is the one that is most linked to delivery of steroid-based molecules for the production of hormones within the body, both the steroid hormones and the sex hormones. And that's really important as well because there's all sorts of talk about our medications which lower low-density lipoprotein, LDL cholesterol, having an impact on... the formation of hormones within the body? Well, because most of our medications don't actually affect high-density lipoprotein, then based on a scientific premise, it's very unlikely that lowering LDL cholesterol has much of an impact at all on formation of the steroid hormones. So just an interesting aside and one to fit in there. This has been a really difficult subject to cover. I've really wanted to get across that some of these important building blocks, some of these important lipid compounds within the body need to be moved through particular particles. And those particles mean that the lipids can move through water or serum. These particular particles vary depending on how much payload, how much fatty centre they've got. The more fatty centre in them. bigger the particle, the lower the density. As these particles give up their central core, the density increases. Most of the particles give up their cholesterol central core as they travel around the body. High density lipoprotein gives up cholesterol mainly for the hormone producing organs, but it's also able to take up cholesterol and triglyceride from peripheral tissues and bring it back to the core of the body. I touched on apoproteins. These are these fantastic proteins that can stick outside the sphere of our lipoprotein particles and therefore allow these things to move around in water, but at the inside, they're holding our triglycerides and holding our cholesterol esters they're holding our water repellent compounds which is pretty cool i talked about some of those apoproteins and their particular designation so that they can lock in to specific tissues based on exactly what the protein is and what the receptor is on the organ well i hope i've covered some stuff that fills in some of the gaps and explains some of the terminology you've heard. I'm hoping you understand that we start off with really big particles. The biggest particles for fat transport come from the intestine, from when we've just eaten a fatty meal, of course. But then the body can produce large particles. We start with the chylomicron from the intestine, but the liver can produce very low-density lipoproteins given the right substrate. These particles move around the body. They give up their fatty payload. They become more and more dense as they do so. The whole process is one of shifting, moving, and recycling. LDL cholesterol is our low-density lipoprotein, so every time you hear that LDL... which is the one that we talk about a lot. We're talking about low-density lipoprotein. It's apoprotein. Its particular hook, if you like, is ApoB100 or apoprotein B. We very quickly mentioned apoprotein lowercase a or little a, and we will talk about him on another day. When we've touched on HDL cholesterol and the role it has, which is... quite specific compared to the other cholesterol lipoprotein particles which give up their payload whereas HDL, high density lipoprotein can take up the fatty payload and take it back to the central parts of the body, the liver. Okay, well, I hope that's made some sense. I hope I haven't given you too many questions. If you do have any questions, drop us a note. If you've got any suggestions for future presentations, please let me know. As always, I wish you the very best, and please don't die from a heart attack. Goodbye. You have been listening to another podcast from Dr. Warrick. Visit his website at drWarrickbishop.com for the latest news on heart disease. If you love this podcast, feel free to leave us a review.
