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How Does The Liver Make Cholesterol

How Cholesterol Moves Around The Body

“Bad” Cholesterol Makes a HEALTHY Liver

Cholesterol is a white, insoluble and waxy substance. It is carried around the body by two key transport systems in the blood, which include:

  • Low-density lipoprotein cholesterol carries most of the cholesterol that is delivered to cells. It is called the bad cholesterol because when its level in the bloodstream is high, it can clog up your arteries.
  • High-density lipoprotein cholesterol is called the good cholesterol, because it helps remove excess cholesterol out of the cells, including cells in the arteries.

What Happens To The Newly

First, you could try to burn this fat for energy. However, with all the available glucose around after the meal, there is simply no reason for the body to burn the new fat. Imagine that you have gone to Costco and simply bought waaayyy too much food to store in your refrigerator. One option is to eat it, but theres simply too much. If you cannot get rid of it, much of the food will be left on the counter where it will rot. So this option is not viable.

The only option left is to transfer this new created triglyceride somewhere else. This is known as the endogenous pathway of lipid transport. Triglycerides are packaged together with special proteins called very low-density lipoproteins . These packages can now be exported out to help decompress the congested liver.

The amount of VLDL produced mostly depends upon the availability of hepatic triglycerides. Lots of newly created fat triggers production of more of these triglyceride filled VLDL packages. Insulin plays a key facilitating role in the production of VLDL, by increasing the genes needed for DNL. Experimental infusion of large amounts of carbohydrates increases the release of VLDL from the liver by a massive 3.4 fold. This massive increase in triglyceride rich VLDL particles is the major reason for an increased plasma triglyceride level, detectable in all standard blood test for cholesterol.

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What Causes High Cholesterol

Three major things contribute to high cholesterol levels:

  • diet: eating a diet high in fats, particularly saturated fat and trans fat
  • heredity: having a parent or close family member with high cholesterol
  • obesity: having a poor diet and not exercising
  • People who are physically active, eat healthy foods, don’t have a family history of high cholesterol or heart disease, and aren’t overweight are less likely to have high cholesterol.

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    If Cholesterol Is Necessary Why Do We Have To Worry About How Much We Have

    Having enough cholesterol to meet your needs is important. Having too much cholesterol can cause problems. If your cholesterol levels are high, the condition is called hypercholesterolemia. If your cholesterol levels are low, the condition is called hypocholesterolemia. It is not common to have cholesterol levels that are too low, but it can happen.

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    What Are Normal Levels Of Cholesterol

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    Normal levels of cholesterol are different depending on your age and sex. These guidelines show desirable total, non-HDL,LDL and HDL levels by age and sex.

    Table 1: Target cholesterol levels by age and sex

    Age and sex

    cholesterol

    cholesterol

    People aged 19 years and younger Men aged 20 years and olderWomen aged 20 years and older

    The table above spells out the numbers for normal cholesterol levels. The table below shows you cholesterol levels that are higher than normal. High cholesterol numbers vary by age group and sex, and may be different for those who have heart disease. These guidelines represent high cholesterol numbers for those who do not have heart disease.

    Table 2: High total, non-HDL and LDL cholesterol levels by age and sex

    Age and sex
    People aged 19 years and younger

    Borderline: 170-199 mg/dL

    High: Greater than or equal to 200 mg/dL

    Borderline: 120-144 mg/dL

    High: Greater than or equal to 145 mg/dL

    Borderline: 110-129 mg/dL

    High: Greater than or equal to 130 mg/dL

    High: Greater than or equal to 239 mg/dL

    Near optimal or above optimal: 100-129 mg/dL

    Borderline high: 130-159 mg/dL

    Very high: Greater than 189 mg/dL

    High: Greater than or equal to 239 mg/dL

    Near optimal or above optimal: 100-129 mg/dL

    Borderline high: 130-159 mg/dL

    Very high: Greater than 189 mg/dL

    LDL cholesterol levels

    If you do not have heart disease or blood vessel disease, and you are not at high risk for developing heart disease, the optimal number is less than 100 mg/dL.

    Triglycerides

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    Why Should I Lower My Cholesterol

    Evidence strongly indicates that high cholesterol can increase the risk of:

    This is because cholesterol can build up in the artery wall, restricting the blood flow to your heart, brain and the rest of your body. It also increases the risk of a blood clot developing somewhere in your body.

    Your risk of developing coronary heart disease also rises as your blood’s cholesterol level increases. This can cause pain in your chest or arm during stress or physical activity .

    How Do You Prepare For A Cholesterol Test

    In most cases, youll need to fast for nine to 12 hours before the test. Make sure you tell the person drawing your blood how long it has been since you ate or drank anything that wasnt water.

    There are some cases when a cholesterol test is done without fasting. This is true for tests done at health screenings and may be true for people younger than 20 or for people who are unable to fast.

    Some medical societies believe that fasting is not necessary to get a true picture of lipid levels in the blood, while other associations stand by the belief that fasting gives a better idea of a persons heart disease risk. You should be clear on whether or not you need to fast, and for how long, before you go for the blood test.

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    Why Is High Cholesterol So Important

    There appears to be an association between elevated cholesterol and risk of premature death from cardiovascular disease.

    210 mg/dl is the average cholesterol level for those in developed countries. This level predicts a 50% chance of premature death due to atherosclerosis. Bummer.

    Going from 200 mg/dl to 260 mg/dl bumps up chance of death by 500%. The Framingham study showed that no one has died of cardiovascular disease while having a cholesterol level below 150 mg/dl.

    Just getting blood cholesterol right under 200 mg/dl might not be enough. 35% of heart attacks that occurred in the Framingham study were in those with normal cholesterol, between 151 mg/dl and 200 mg/dl.

    Some have argued that the association between cholesterol and cardiovascular disease, part of a theory of heart disease known as the lipid hypothesis, is minimal at best.

    Still, other experts have stated that maintaining a low cholesterol level can protect us against cardiovascular disease.

    Regularly maintaining a cholesterol level of less than 150 mg/dl makes one practically heart attack proof and insures against further progression of the disease.Dr. Caldwell Esselstyn

    Gosh, it seems like lower is always better. Not so fast.

    Some data indicate that low cholesterol levels are associated with depression and cerebral hemorrhage.

    While cholesterol seems to play an important role in cardiovascular disease, its definitely not the only factor involved.

    What Kind Of Test Measures Cholesterol

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    Everyone over the age of 20 should get their cholesterol levels measured at least once every five years. Your healthcare provider will order a blood test that will indicate how much cholesterol is carried in your bloodstream. This test will give your cholesterol levels. Your provider might also order what is called a lipid panel or a lipid profile. The panel gives you the following numbers:

    • Total cholesterol.
    • Non-HDL cholesterol.
    • Ratio between cholesterol and HDL.

    There are advanced tests that break down the size and shapes of LDL cholesterol levels, and also give the LDL particle number, but those are not normally ordered. Some test makers say that the more advanced tests are better at indicating who is at risk for heart disease, but most providers still feel that the usual tests are adequate.

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    Various Fates Of Cholesterol In The Liver

    In the liver, cholesterol has three major fates: conversion to bile acids, secretion into the bloodstream , and insertion into the plasma membrane. Conversion of cholesterol to cholic acid, one of the bile acids, requires about 10 enzymes. The rate of bile synthesis is regulated by the first enzyme of the pathway, cholesterol 1α-hydroxylase, one of the cytochrome P450 enzymes . Cholesterol, mainly in the form of cholesteryl esters, is exported to other organs, after packaging in particles called very-low-density lipoproteins. Synthesis of cholesteryl esters is catalyzed by acyl CoA:cholesterol acyltransferase, a membrane-bound enzyme of the ER. Free cholesterol is used in membrane synthesis, where it appears as part of the walls of vesicles in the cytoplasm. These vesicles travel to the plasma membrane, where subsequent fusion results in incorporation of their cholesterol and phospholipids into the plasma membrane.

    D.R. Arnold, P.O. KwiterovichJr, in, 2003

    Researchers Identify Liver Pathway Linked To Negative Impacts Of High

    ANN ARBORIt’s no secret that a high-fat, high-cholesterol “junk food” diet has been linked to major health problems, including high blood cholesterol and the buildup of plaques in the arteries, known as atherosclerosis.

    Research led by the University of Michigan Life Sciences Institute has identified a pathway in the liver, controlled by a protein known as BAF60a, that contributes to these negative effects by stimulating the production of bilewhich helps the body to absorb more cholesterol and other fats from the foods we eat.

    Mice genetically engineered to have livers lacking BAF60a had cholesterol levels about 40 percent lower than normal mice when both were fed a junk food diet, according to findings published Nov.12 in Cell Reports.

    “From a basic science perspective, we are continuing to learn about how several variants of BAF60 play different important roles in metabolic regulation in diverse cell typesfat, muscle, liver,” said study senior author Jiandie Lin, a faculty member at the LSI, where his lab is located. “And this latest research uncovers a new pathway in the liver that may point the way toward new therapeutic approaches to lowering cholesterol and reducing the risk of atherosclerosis.”

    The mice were fed a specially formulated diet high in fat and sugar to simulate a bad “Western diet.” About 40 percent of calories came from fat and another 40 percent from sugar.

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    How Often To Have A Test

    The American Heart Association recommends that people without a family history of heart disease or other risk factors check their cholesterol levels once when they are aged 911 years and again when they are aged 1721 years.

    After the age of 20 years, the AHA suggests that people recheck their cholesterol levels and other risk factors every 46 years, as long as the risk remains low.

    Those with a family history of heart disease should speak with a doctor about how often they need a cholesterol test.

    Regulation Of Hepatic Cholesterol

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    The intracellular level of hepatic cholesterol is regulated by modulation of 3-hydroxy-3-methylglutarylâcoenzyme A reductase, the rate-limiting enzyme in cholesterol biosynthesis, and by three separate integrated lipoprotein regulatory cycles . An increase in the hepatic level of cholesterol results in a decrease in cholesterol synthesis and a coordinate response in the three separate lipoprotein cycles. In the first cycle, the level of cholesterol can be reduced by increased secretion of cholesterol-enriched VLDL, which is converted to IDL and finally cholesterol-enriched LDL, and by a decrease in the level of LDLR expression reducing LDL uptake by the liver . An increase in hepatic cholesterol results in an up-regulation of the LXR/RXR transcription factors, resulting in an increase in the level of the ABCA1 transporter this would enhance hepatocyte cholesterol efflux to lipid-poor apoA-I with the formation of pre-ò-HDL and conversion to ñ-HDL following cholesterol esterification by LCAT . The up-regulation of the LXR pathway would also increase gene expression of ABCG5 and ABCG8,61,62 which facilitates the secretion of cholesterol from the hepatocyte into the bile and would also increase the efflux of intracellular cholesterol in the enterocyte back into the lumen of the gastrointestinal tract, thereby decreasing the delivery of cholesterol back to the liver via the enterohepatic circulation61,62 .

    Makoto Makishima, Sachiko Yamada, in, 2018

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    Hepatic Cholesterol Ester Storage Disease

    Hepatic cholesterol ester storage disease is associated with acid esterase activity in the liver decreased to values between 10% and 30% of normal. The liver shows similar lipid accumulation to that of Wolman’s Disease with 50% of cases having increased fibrosis. The clinical presentation is usually asymptomatic hepatomegaly noticed at a median age of 3 years . One-third of patients develop splenomegaly and variceal bleeding has been recorded. Hypertriglyceridaemia and hypercholesterolaemia are found in the majority. Standard biochemical tests of liver function are usually mildly abnormal. The long-term prognosis is uncertain, but death from liver failure has occurred at 18 years of age and one patient underwent liver transplantation for hepatic failure at 14 years of age. Suppression of cholesterol and apolipoprotein B synthesis by HMG-CoA reductase inhibitors may be beneficial.

    Shih-Chang Chuang, … King-Teh Lee, in, 2013

    Dietary Cholesterol And Liver Disease

    Youâve probably heard that eating too much cholesterol is bad for your heart. But it may be even worse for your liver.

    Cholesterol from food mostly ends up in the liver. If you are getting too much, this can increase your risk for fatty liver disease. High cholesterol also can turn fatty liver disease into a more serious and sometimes fatal condition known as nonalcoholic steatohepatitis .

    When fatty liver disease turns into NASH, it can lead to other liver problems including:

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    Kupffer Cell And Stellate Cell Activation

    Cholesterol crystals may trigger the inflammatory response in THP macrophages27 or primary Kupffer cells,26 phagocytosing lipid droplets of apoptotic or necrotic hepatocytes. Lipolytic enzymes released in the zone of inflammation may release cholesterol from cholesterol esters and thereby enhance cholesterol crystal formation .2). Transwell experiments showed that direct contact and phagocytosis of the crystals was mandatory. Cholesterol crystals can activate the NLRP3 inflammasome and thereby promote the activation of IL-1 and IL-18 from their precursors. Consequently, inhibition of the NLRP3 inflammasome reduced the severity of liver inflammation and fibrosis in genetic or diet-induced mouse models of NASH.64 Cholesterol has been shown to favor the transdifferentiation of hepatic stellate cells into myofibroblasts 2) and thereby might contribute to the development of hepatic fibrosis.65

    Your Liver And Cholesterol

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    Your liver does much more than you probably give it credit for. Not only does it prevent you from dying every time you have a little too much to drink at Happy Hour, but its central to the overall structure and function of your cells, and it also plays an important role in the creation and management of cholesterol. In fact, your liver produces the vast majority of cholesterol in your body, and if youre living with familial hypercholesterolemia, you can also blame your liver for the difficulty in keeping your excessive cholesterol levels under control. Yes, the liver and cholesterol go hand in hand, but what does that mean for you in terms of cholesterol management?

    Your Liver and Cholesterol A Complex Relationship

    The liver synthesizes cholesterol for export to other cells, but its also instrumental in removing cholesterol from the body. It does this by converting the cholesterol to bile salts and transferring the compounds into the bile, where they are ultimately expelled from the body. In addition, your liver synthesizes most of the necessary lipoproteins needed to transport cholesterol and lipids throughout your body. These processes allow you to manage your cholesterol and maintain a healthy heartassuming that your liver is doing its job.

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    Increase Your Physical Activity

    Physical activity increases levels of HDL cholesterol the good cholesterol that removes LDL cholesterol from the blood. Vigorous aerobic exercise is best.

    If you havent been exercising much lately, gradually build up to the recommended amount of physical activity:

    • People aged 18-64 years should do 30 to 60 minutes of moderate-intensity physical activity on most days of the week.
    • People aged 65 years and over should aim for a total of 30 minutes of moderate physical activity on most days .

    Moderate-intensity exercise is a level that increases your heart rate and breathing but allows you to keep talking. Vigorous intensity exercise makes your heart rate higher and makes you breathe more heavily.

    Resistance training and muscle-toning exercises can increase HDL cholesterol. Aim to do this twice a week.

    Effects Of High Cholesterol Levels

    The liver is the main processing centre for cholesterol and dietary fat. When we eat animal fats, the liver transports the fat, together with cholesterol in the form of lipoproteins, into our bloodstream.

    Too much cholesterol circulating within LDL in our bloodstream leads to fatty deposits developing in the arteries. This causes the vessels to narrow and they can eventually become blocked. This can lead to heart disease and stroke.

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    What Happens To Cholesterol In The Body

    The body carries cholesterol and other types of fat cells, called triglycerides, in the bloodstream.

    Triglycerides are fat storage molecules that circulate around the body and serve as a source of energy. Both triglycerides and cholesterol are insoluble in water. Therefore, they need protein molecules called lipoproteins to transport them around the body in the blood.

    The main types of lipoproteins that the body uses to transport lipids in the body are:

    • Chylomicrons: These large particles transport dietary triglycerides and cholesterol from the intestine to the liver and other body tissues.
    • Very low-density lipoproteins : The liver produces these particles. Muscle and adipose tissues metabolize VLDL into low-density lipoproteins .
    • LDL: Small dense LDL particles carry most of the cholesterol in the bodys circulation to the tissues. LDL enters the arteries, and free radicals can oxidize it, causing atherosclerosis.
    • High-density lipoproteins : These particles play an important role in transporting cholesterol back to the liver, which helps prevent it from being deposited in arteries. HDL has antioxidant and anti-inflammatory properties, which can inhibit atherosclerosis.

    Doctors measure these lipoprotein levels to help them look at a persons overall risk of heart disease and stroke.

    High cholesterol usually causes no symptoms, and the only way that someone can tell if their levels are healthy is to take a blood test.

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