Transcript for:
Chylomicrons and Fat Transport

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 all together 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 these 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 so 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 and so 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 and so 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 so let's say we're traveling this way down the capillary and it turns out that there are enzymes situated in the capillary beds which I'm going to indicate again here by using kind of a Mac man-like character because these enzymes are going to have a role of breaking some of these molecules down and these enzymes are called lipo pro teen lipase and it's a very suggestive name lipoprotein refers to the fact that it's working on a lipoprotein like the chylomicron and the lipase refers to the fact that it serves the same function as a lipase in the small intestine it's essentially going to take the tri acyl glycerides contained in the chylomicron and break them up into individual fatty acids and the way that this occurs is that it turns out that there is a specific type of protein that's on this chylomicron and this specific type of protein when these lipoprotein lipase is see this protein they essentially are activated and they start breaking down these triacylglycerols into individual fatty acids and a free glycerol backbone and so I'm not going to 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 and 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 so 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 and so I'll draw a couple of representative adipose cells and these are specialized cells for storing fat and so they actually have very small nuclei and have just a lot of room in their site Oh them to store fat and so 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 tryi so glycerides 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 remnants on a brave eight here is C R and of course there might still be some triglycerides that weren't you know broken down by lipoprotein lipase and there's also probably some cholesterol in there that was absorbed by your diet as well and so it still contains a lot of useful things for our body and that is why our liver now plays a big role in reabsorbing these chylomicron remnants oh I'm just going to 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 and the way I like to think about the liver is that all roads of digestion lead to the liver and so remember that while fatty acid metabolism while the digestion of these tri acyl glycerides is going on in the small intestine which I'm going to 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 and these are small enough to enter the capillary bed directly and once they enter the capillary bed all of those capillaries eventually funnel into a vein that goes directly to the liver and so 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 and chylomicrons and carry through the lymphatic vessels pass through the liver now you can imagine that after a big meal there's going to be a lot of glucose absorbed that will go through the stain into the liver and 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 a carbohydrate storage fuel that our body has and it stores it directly write in this liver conveniently but if we have a lot of extra glucose there's 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 try acyl glyceride molecules and package them into the specialized protein carrier molecules very similar to the chylomicrons except instead of called chylomicrons these molecules are called v LDL which stands for very low density lipoprotein and refers to the density of protein two 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 V LDL particle and so like I said before it contains basically a protein shell and it packages all of those fat molecules inside of it an addition to the fat molecules 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 and so both of those things can also go into the VLDL molecule and so the liver kind of allows these two pathways to converge now ultimately just like the Chi a micron 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 so I'm just going to 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 so we've successfully followed the journey of our chylomicron remnants 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 and 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 so I'm going to 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 a two main hormones at play and 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 Asians of different enzymes to signal these adipose cells to release all of the fatty acids from these triethyl glyceride molecules into the bloodstream to illustrate that I'm going to 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 what happens immediately upon digesting a meal which we showed on the left side here so as I mentioned the level of hormones signals these cells to release fatty acids so I'm just going to draw a 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 into the bloodstream and so remember these are hydrophobic right and the way the body deals with this is it allows these free fatty acid molecules to travel in an alongside these large proteins in the blood called albumin and these are proteins that are made also by the liver and so these fatty acids travel kind of along these proteins so that they can dissolve essentially in the aqueous environment of the bloodstream and I just want to mention really quickly that the enzyme that catalyzes the breakdown of the tri acyl glycerides in the adipocytes in response to these changing hormone levels so I'm just going to indicate that again by this macman character here has a special name it's called hormone sensitive lipase hormone sensitive lipase so again it's a lipase because it's breaking down a tryi so glyceride and its 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 so 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 these free fatty acids that are floating around in the blood thanks to hormone sensitive 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 and 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 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 and that's because this process of converting glucose to fatty acids is also stimulated by insulin so when the insulin levels drop this process also comes to a halt as well