Digestion, Mobilization, and Transport of Fats - Part II

- [Instructor] Recall that chylomicrons are specialized protein carrier molecules that are packaged in the small intestine with hydrophobic molecules, such as fats, as well as cholesterol, that we digest and absorb in our small intestine, and so shown here are representative fat molecules in yellow surrounded by a protein shell in purple, and altogether this is called a chylomicron. Now, recall that once we form these chylomicrons in the small intestine, they are packaged and then sent off from the small intestine into the lymphatic capillary, called a lacteal next to the small intestine cells, and eventually they will drain into veins via the thoracic duct near our shoulder, and then eventually of course, veins enter the heart and the heart pumps it to the lungs, which reoxygenate the blood, and of course, eventually these chylomicrons will reach arteries, which drain, of course, into capillary beds, which is the site of absorption of these fats by other tissues in the body. To demonstrate how that works, let's go ahead and clear our screen here, and we can go ahead and draw a representative, very zoomed-out version of a capillary here. We know that capillaries are situated next to many different types of tissues, and this is how and where these tissues obtain oxygen as well as nutrients. We want to figure out how do the fat molecules contained within the chylomicron shown here, how are these liberated and absorbed by the surrounding tissues? Let's say we're traveling this way down the capillary and it turns out that there are enzymes situated in the capillary bed, which I am gonna indicate again here by using kind of a Macman-like character because these enzymes are going to have a role of breaking some of these molecules down. These enzymes are called lipoprotein lipase. It's a very suggestive name. Lipoprotein refers to the fact that it's working on a lipoprotein, like the chylomicron, and lipase refers to the fact that it serves the same function as the lipase in the small intestine. It's essentially going to take the triacylglycerides contained in the chylomicron and break them up into individual fatty acids. The way that this occurs is that it turns out that there's a specific type of protein that's on this chylomicron, and this specific type of protein, when these lipoprotein lipases see this protein, they essentially are activated and they start breaking down these triacylglycerides into individual fatty acids and a free glycerol backbone. I'm not gonna write the entire chemical structure, but just kind of symbols to remind ourselves of what is happening. Notably, this enzyme, lipoprotein lipase, is also activated by insulin, which is present in your body in response to an influx of glucose right after a meal. Because glucose and fats are often found together in foods, it seems appropriate that right after a meal, this should also stimulate lipoprotein lipase. Now, nearly all tissues can take up fats and eventually use them to extract ATP from. Notable exceptions are your brain because fatty acids cannot cross the blood-brain barrier, as well as red blood cells which don't contain mitochondria, and mitochondria are very important for the oxidation of fatty acids, which yields ATP. Without mitochondria, we can't extract energy from fats. But muscle, for example, can take up some of these fatty acids, and so it'll see the free fatty acids and it can take these up because they're small enough now, and perhaps the biggest user or biggest absorber of all of these fatty acids in the capillary are adipose cells. I'll draw a couple of representative adipose cells. These are specialized cells for storing fat. They actually have very small nuclei and have just a lot of room in their cytoplasm to store fat. They go ahead and see that these fatty acids are floating around, and so they take up these, and they eventually, to kind of compact them down for storage, turn them back into triacylglycerides and store them as kind of big, fatty droplets inside of their cells. Now, let's return to the chylomicron. Once it's been digested by the lipoprotein lipase, at the end of its journey through the capillary bed, we call whatever's left, we call it a chylomicron remnant, which I'll abbreviate here as CR. Of course, there might still be some triacylglycerides that weren't broken down by lipoprotein lipase, and there's also probably some cholesterol in there that was absorbed by our diet as well. It still contains a lot of useful things for our body. That is why our liver now plays a big role in reabsorbing these chylomicron remnants. I'm just gonna draw kind of a representative liver here, not really drawing anything in the right anatomical position, but just to kind of give you an overview. The liver contains specific receptors to take up these chylomicron remnants. Now, you might be wondering why the liver? Why does the liver reuptake these chylomicron remnants? Why not some other organ? The way I like to think about the liver is that all roads of digestion lead to the liver. Remember that while fatty acid metabolism, while the digestion of these triacylglycerides is going on in the small intestine, which I'm gonna kind of just draw representatively here, in this pink line here, we also have the breakdown and absorption of carbohydrates and proteins and nucleic acids as well. These are small enough to enter the capillary bed directly. Once they enter the capillary bed, all of those capillaries eventually funnel into a vein that goes directly to the liver. That is a very important anatomical connection because it means that everything that's digested and absorbed in the small intestine, except for fats, which, remember, are carried in chylomicrons and carried through the lymphatic vessels, pass through the liver. Now, you can imagine that after a big meal, there is going to be a lot of glucose absorbed that will go through this vein into the liver. Some of this glucose will be used to make ATP and some of it will be used to build glycogen, which, remember, is the main form of carbohydrate storage fuel that our body has, and it stores it directly right in this liver conveniently. But if we have a lot of extra glucose, there is actually a metabolic pathway that allows us to convert glucose into more fatty acids. Now, this is where I think the cool part really comes in. The liver has a similar functionality to the small intestine. It can package these fatty acids into triacylglyceride molecules and package them into the specialized protein carrier molecules, very similar to the chylomicrons. Except instead of called chylomicrons, these molecules are called VLDL, which stands for very low density lipoprotein and refers to the density of protein to hydrophobic molecules inside of it, which isn't too relevant for this discussion, but just so that you're aware of the name, this is called a VLDL particle. Like I said before, it contains basically a protein shell and it packages all of those fat molecules inside of it. In addition to the fat molecule that it's packaging that have been newly made by the liver from the glucose, it also, remember, the liver was also taking up these chylomicron remnants, which also might have contained remaining fat molecules as well as cholesterol. Both of those things can also go into the VLDL molecule. The liver kind of allows these two pathways to converge. Now, ultimately, just like the chylomicron left the small intestine and traveled all the way to the capillary beds so that the lipoprotein lipase could release the fatty acids. The VLDL molecule has a very similar fate. I'm just gonna put an asterisk here, by this capillary bed here, to remind you that the VLDL, once it reaches the capillary bed, will essentially, it can be acted upon by the lipoprotein lipase again. In addition, it also releases cholesterol to cells, but that's something that we won't cover in this video. We've successfully followed the journey of our chylomicron remnant from our small intestine to the liver and simultaneously how fat is transported and stored inside of our adipose cells, which I will now actually label so that we don't forget what these are. But there's one more question that we need to answer before we finish, which is what happens to the fat that's stored in these adipose cells? Now, it turns out that these adipose cells have hormone receptors on their cell surfaces which can detect the levels of hormones that are circulating inside of the body. This is important because, remember that the major hormone that's floating around right after we've eaten a meal is insulin. But a couple hours after a meal, or even several hours after a meal, the levels of insulin begin to fall. I'm gonna write that. After a meal, the levels of insulin decrease and the levels of a different hormone called glucagon begin to increase in response to not having enough blood glucose. There are also several other hormones that are elevated during this time as well, but these are kind of the two main hormones at play. The decrease in the level of insulin as well as the increase in the level of glucagon can both stimulate these hormone receptors, and what that does is, it sends a signal inside of these cells through various modifications of different enzymes to signal these adipose cells to release all of the fatty acids from these triacylglyceride molecules into the bloodstream. To illustrate that, I'm gonna go ahead and draw another kind of blown-up version of a capillary bed next to all of these adipose cells to illustrate what happens after, several hours after eating a meal, in contrast to what happens immediately upon digesting a meal, which we showed on the left side here. As I mentioned, the level of hormones signals these cells to release fatty acids. I'm just gonna draw kind of representative symbols for fatty acids, and they will diffuse down their gradient, because of course the blood now has low levels of fatty acids traveling through it and to the bloodstream, and so, remember, these are hydrophobic, right? The way the body deals with this is it allows these free fatty acid molecules to travel in and alongside these large proteins in the blood called albumin. These are proteins that are made also by the liver. These fatty acids travel kind of along these proteins, so that they can dissolve, essentially in the aqueous environment of the bloodstream. I just want to mention really quickly that the enzyme that catalyzes the breakdown of the triacylglycerides in the adipocytes in response to these changing hormone levels, so I'm just gonna indicate that again by this Macman character here, has a special name. It's called hormone-sensitive lipase. Hormone sensitive lipase. Again, it's a lipase because it's breaking down a triacylglyceride, and it's hormone-sensitive because it responds to these changing levels of hormones. Now, returning to the fatty acids that are now traveling in the blood, most tissues in the body can now take these up. Again, we have muscle cells. My kind of bad drawing of a muscle here, and some heart cells, perhaps, along with other tissues in the body. Remember, notable exceptions are the brain and the red blood cells, but most tissues can take up these fatty acids and produce a lot of ATP from them to kind of sustain them when they don't have an immediate influx of maybe fuel right after a meal. Now, finally, I want to mention that one of the biggest consumers of the three fatty acids that are floating around in the blood thanks to hormones instead of lipase, is the liver, and that is because during the time of fasting, after a meal, when the body needs to maintain blood glucose levels for the brain and the red blood cells, for example, that cannot use these fatty acids, the process of gluconeogenesis or the creation of new glucose, which occurs largely in the liver, requires a lot of ATP. The only fuel that the body has to create this ATP, the major fuel at least, are fats, and so the liver will take a lot of these fats and break them down to the produce the ATP necessary to support gluconeogenesis. In addition, because we don't want to waste any of the glucose that's producing gluconeogenesis, this process of converting glucose into fatty acids is also halted when the levels of insulin fall. That's because this process of converting glucose to fatty acids is also stimulated by insulin. When the insulin levels drop, this process also comes to a halt as well.