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Steroids and Bile Acids: Movement of Cholesterol

by Kevin Ahern, PhD
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    00:01 Now this figure shows the movement of cholesterol in the body and it's a little complicated but I think that you will see some general themes.

    00:11 Let's consider dietary cholesterol first. Starting on the right dietary lipids come into your digestive system.

    00:17 This include fats, includes fats soluble vitamins; it includes cholesterol and related compounds.

    00:24 These pass through the intestinal wall into the lymph system actually where they are packaged up into chylomicrons.

    00:33 So these very insoluble substances that I just described are packaged almost immediately upon leaving the digestive system.

    00:40 The chylomicrons are the biggest, fluffiest complexes that are lipoprotein complexes that ultimately make into the blood stream.

    00:50 So these complexes contain the very water insoluble compounds the fats, the fat soluble vitamins and the cholesterol.

    00:59 And chylomicron's job is to get them into the blood stream where they travel.

    01:04 And they then go through the blood stream and hit the tissues.

    01:08 When the chylomicrons hit the tissues something happens. Now, you might think that the chylomicrons they are really big. They are actually the biggest complexes involved in carrying these things.

    01:18 You might thing these are associated with atherosclerosis, they are not.

    01:22 So these guys are traveling in the blood stream and they hit the capillaries where they get stuck; because, they are so big.

    01:29 And what happens with the capillaries is that the capillaries have enzymes that literally peel the inside of the material in the chylomicron away and eat those nutrients.

    01:40 So the cells will be taking fat, they will be taking fat soluble vitamins out of the chylomicrons.

    01:46 They don't take cholesterol out, by the way, and the chylomicrons will shrink creating what are called chylomicron remnants.

    01:54 Now every thing that you see in green on the screen is happening in the blood stream.

    01:59 The chylomicron remnants are at the capillaries and they become small enough that they can pass through the capillary.

    02:07 And when that happens they travel back to the liver.

    02:11 And the liver has a receptor that grabs the chylomicron remnants and it takes all the stuff inside of them and all that stuff inside of them it has to package and put it away somewhere.

    02:20 That includes the fat, a fat soluble vitamins and the cholesterol.

    02:24 Well you can see that we start overloading the liver with some of this stuff and we might have some problems.

    02:30 And that's why dietary considerations are important in monitoring cholesterol levels.

    02:34 Cholesterol and fat, however, are needed by the body and we have seen in other lectures how the liver plays a role in maintaining glucose levels that are reasonably constant level.

    02:47 The liver is also involved in maintaining fat and hopefully cholesterol levels in the same way.

    02:53 Now this happens through a sensing mechanism that the liver uses. That is a little complicated. So let me tell you how this works.

    03:01 When the liver senses that there is a need in the body for some of the materials I have just described it says "Okay, I am gonna package these up".

    03:10 And it packages it up in the form of what are called VLDLs.

    03:15 So the VLDLs released by the liver contain the fats, the fatty acids and cholesterol.

    03:20 And what the VLDLs is do they go back out into the blood stream where a similar process happen like with a chylomicrons. The cells grab them and start taking this away.

    03:30 Well the VLDLs become the IDLs known as the intermediate density lipoproteins.

    03:35 And again cholesterol hasn't been taken out of them.

    03:39 So the goodies are being taken away.

    03:43 The lipoprotein complexes are shrinking which is why they are going from very low density to intermediate density.

    03:49 And the intermediate density go to the low density lipoprotein complexes or the LDLs.

    03:54 Now the LDLs have the highest concentration of cholesterol.

    04:00 And the LDLs also are the most likely to be oxidized by reactive oxygen species that are present in the blood stream.

    04:08 Now reactive oxygen species are the problem.

    04:11 They are problem; because, they react without the control of enzymes.

    04:15 And when you have reactions that are out of control, unpredictable things can happen.

    04:21 Well one of the unpredictable things that can happen is the LDL can actually get damaged and become attached to part of an artery.

    04:30 When that happens the immune system can recognize that damage LDL as a problem and attack it.

    04:36 And then more of the immune system can attack it and this attack can continue and we can create a process what's known as a foam cell; because, it looks big and foamy.

    04:47 Well this can involve the binding of other LDLs; because, the immune system is now recognizing all these LDLs of this complex and this can be the start of the formation of an atherosclerotic plaque.

    04:59 So it's not the cholesterol per se that's causing the problem.

    05:03 The cholesterol is more of an indicator of the problem associated with the LDLs. But nonetheless the accumulation of LDLs causes this problem. So the higher a person's LDL level is, the more likely they are to form atherosclerotic plaque.

    05:17 They might wonder about the reactive oxygen species. Where do they come? Well they come from some normal cellular processes which we can't control. But there are some things that we can control that produce the reactive oxygen species. One of those is smoking cigarettes.

    05:32 Smoking cigarettes will increase levels of reactive oxygen species. And increasing levels of reactive oxygen species has very detrimental effects on health.

    05:42 Now we have gotten to the LDLs and most LDLs of course don't get oxidize. They actually make it back to the liver and this is how the liver actually does the sensing.

    05:54 So liver has on its surface, receptors.

    05:57 And the liver tries to monitor what the level of concentration of LDLs actually is.

    06:04 And if the liver senses that the LDL level is too low, then the liver knows that the things it has been sending out need to be increased.

    06:14 So if it senses too low of a level of LDL it says "Okay let's put out more VLDLs; because, everything I am putting out is being eaten." In the ideal world if the LDL level is high the liver says "Okay don't put out so much" and then the LDL level drops accordingly. So we could see how this system sort of helps to control itself if it's working properly.

    06:37 If there are disruptions to the way that the LDL signal is being perceived then there can be some pretty significant problems. Familiar hypercholesterolemia occurs when a person has a defective LDL receptor.

    06:51 Then the liver doesn't get any signal for example that their LDL level isn't coming back at all. So the liver as far as it concerned, "Everything I am putting out is not coming back. Put out more! Put out more!" So people who have this genetic disease tend to have very extremely high levels of cholesterol and many of them die before they become teenagers. So pretty serious consequences associated with cholesterol metabolism.

    07:17 Okay, so as I have said, the liver plays a very important role in modulating lipid levels.

    07:22 It has limitations of capacity. So, if you overload the liver the liver is gonna have a hard time maintaining this and this is why maintaining and monitoring diet is important.

    07:33 So the one lipoprotein complex I haven't talked about it are the HDLs or the high density lipoproteins.

    07:39 Now the high density lipoproteins interestingly are what people called the good cholesterol.

    07:44 So the good cholesterol is involved in scavenging damage. It's involved in scavenging cholesterol and things that haven gotten deposited along the way that really shouldn't have been deposited where they were deposited.

    07:57 Your doctor, if you go to your doctor and check your cholesterol levels, if your HDL levels are high your doctor will be happy; because, that means that a lot of the garbage is being taken care of and been taken back to the liver where it needs to be.

    08:09 So the yin and the yang of cholesterol are LDL is bad, HDL is good; although, that's quite a simplification.


    About the Lecture

    The lecture Steroids and Bile Acids: Movement of Cholesterol by Kevin Ahern, PhD is from the course Lipid Metabolism.


    Included Quiz Questions

    1. HDLs are the smallest
    2. LDLs carry the most fat
    3. Chylmicrons are made by the liver
    4. VLDLs are the densest
    1. Hypercholesterolemia is caused by the absorption of higher concentrations of fats, fat-soluble vitamins, and cholesterol from the small intestine by the fat cells
    2. Hypercholesterolemia arises due to genetic abnormalities in APOB, LDLRAP1, and PCSK9 genes
    3. Hypercholesterolemia is characterized by the presence of high levels of cholesterol and LDL in the bloodstream of the affected individual
    4. In the hypercholesterolemia-affected person, the LDL signal-detecting receptors are usually defective, so the liver can’t sense the levels of LDL in the bloodstream
    5. Hypercholesterolemia is an asymptomatic disorder; however, the prolonged elevation of cholesterol levels in the bloodstream leads to hardening of the arteries
    1. Atherosclerotic plaques
    2. Hypocholesterolemia
    3. Duchenne muscular dystrophy
    4. Down syndrome
    5. Polycystic kidney disease
    1. The high-density lipoproteins send a signal to liver cells to start the transportation of cholesterol from the stock of the stored fats to the various parts of the body
    2. Low-density lipoproteins, when present at high levels, accumulate in the artery wall and get oxidized under the effect of reactive oxygen species
    3. The oxidized LDLs are taken up by foam cells and lead to the development of atherosclerosis
    4. High-density lipoproteins counteract atherosclerosis by removing cholesterol from foam cells
    5. As HDLs inhibit the oxidation of LDLs by reactive oxygen species, so they are considered good cholesterol

    Author of lecture Steroids and Bile Acids: Movement of Cholesterol

     Kevin Ahern, PhD

    Kevin Ahern, PhD


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