Plasma lipid transport - Role of HDL

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By Philip J. Barter, MD, MBBS, FRACP, PhD, Professor and Director, the Heart Research Institute, Sydney, Australia.

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  • Cholesterol of dietary origin is taken up by the liver where it combines with cholesterol newly synthesised in the liver. This cholesterol is subsequently esterified. Triglyceride is formed in the liver either from newly synthesis fatty acids or from free fatty acids (FFA) released from adipose tissue. The cholesteryl esters and triglyceride are incorporated into VLDL.
  • The VLDL (and the cholesterol they contain) are subsequently secreted into plasma.
  • Once in plasma the triglyceride in VLDL is broken down by lipoprotein lipase, releasing free fatty acids for uptake by tissues.
  • As it loses its triglyceride, the VLDL particle becomes progressively smaller and, in a complex series of reactions, is ultimately converted into a triglyceride-poor, cholesterol-rich LDL particle.
  • The cholesterol in LDL is subsequently delivered to tissues following binding of the particles to LDL receptors. Since the level of expression of the LDL receptor is increased in cells that are depleted of cholesterol and decreased in cells that are overloaded with cholesterol, this process ensures that the cholesterol in LDL is delivered precisely where it is needed, whether this is a return of the cholesterol to the liver or an uptake of cholesterol by cells in extrahepatic tissues.
  • New synthesis also contributes to cellular cholesterol.
  • Only the liver and those endocrine tissues that synthesise steroid hormones have the ability to metabolise the cholesterol molecule. Other tissues are totally dependent on an efflux to acceptors in the extracellular space to remove their surplus cholesterol. The predominant extracellular acceptors are HDLs. There are at least three distinct processes (mediated by activities of ABCA1, ABG1 and SR-B1) that promote the efflux of cholesterol from cells. Lecithin:cholesterol acyltransferase (LCAT) esterifies cholesterol on the surface of HDL particles in a process that moves the cholesterol into the inside of the particle.
  • Once the cholesterol has been transferred from cells to HDLs in the extracellular space, it may be delivered to the liver in a process involving binding of HDLs to SR-B1.
  • The cholesterol taken up by the liver may be recycled into VLDL.
  • The cholesterol taken up by the liver may also be released into bile, either as unchanged cholesterol or after being converted into bile acids.
  • In some species, including humans, non-human primates and rabbits, the cholesterol in HDL may also be delivered to the liver by an indirect pathway involving the cholesteryl ester transfer protein-mediated transfer of HDL cholesteryl esters to the VLDL/LDL fractions, with delivery to the liver then being achieved by the receptor-mediated uptake of LDL.
  • In diabetes and the metabolic syndrome there is an increase in release of free fatty acids (FFA) from adipose tissue. A proportion of this is taken up by the liver and converted into triglyceride.
  • This leads to an increased synthesis and secretion of VLDL and an increase in concentration of VLDL triglyceride in plasma.
  • There is also a decreased activity of lipoprotein lipase resulting in a decreased rate of breakdown of triglyceride and a further increase in the concentration of triglyceride in plasma.
  • A decrease in delivery of cell cholesterol to HDL has the capacity to decrease the concentration of HDL cholesterol.
  • An increase in the cholesteryl ester transfer protein-mediated transfer of cholesterol from HDL to the expanded VLDL pool further reduces the concentration of HDL cholesterol.
  • Plasma lipid transport - Role of HDL

    1. 1. Plasma Lipid Transport Role of HDL Philip Barter, MBBS, FRACP, PhD Professor and Director The Heart Research Institute, Sydney, Australia
    2. 2. Plasma Lipid Transport CE FC TG CE: cholesteryl ester FC: free cholesterol FFA: free fatty acids TG: triglycerides FFA Liver Adipose tissue
    3. 3. Plasma Lipid Transport CE FC TG TG CE: cholesteryl ester FC: free cholesterol FFA: free fatty acids TG: triglycerides FFA CE Liver VLDL Adipose tissue
    4. 4. Plasma Lipid Transport CE FFA LPL FC TG TG CE: cholesteryl ester FC: free cholesterol FFA: free fatty acids LPL: lipoprotein lipase TG: triglycerides FFA CE Liver VLDL Adipose and other tissues Adipose tissue
    5. 5. Plasma Lipid Transport CE FC TG CE TG TG TG FFA LPL CE: cholesteryl ester FC: free cholesterol FFA: free fatty acids LPL: lipoprotein lipase TG: triglycerides FFA CE Liver LDL VLDL Adipose tissue Adipose and other tissues
    6. 6. Plasma Lipid Transport CE FC TG CE LDL receptor LDL receptor TG TG TG FFA LPL CE: cholesteryl ester FC: free cholesterol FFA: free fatty acids LPL: lipoprotein lipase TG: triglycerides FFA CE CE Liver LDL Liver Cell in peripheral tissue VLDL Adipose tissue Adipose and other tissues
    7. 7. Plasma Lipid Transport CE FC TG New synthesis FC LDL receptor LDL receptor TG TG TG FFA LPL CE: cholesteryl ester FC: free cholesterol FFA: free fatty acids LPL: lipoprotein lipase TG: triglycerides FFA CE CE CE Liver LDL Liver Cell in peripheral tissue VLDL Adipose tissue Adipose and other tissues
    8. 8. Plasma Lipid Transport CE FC TG TG New synthesis LDL receptor LDL receptor CE TG TG TG CE: cholesteryl ester FC: free cholesterol FFA: free fatty acids LCAT: lecithin cholesterol acytransferase LPL: lipoprotein lipase TG: triglycerides TG FFA LPL LCAT FFA CE CE CE FC Liver HDL LDL Liver Cell in peripheral tissue VLDL Adipose tissue Adipose and other tissues
    9. 9. Plasma Lipid Transport CE CE FC TG TG New synthesis LDL receptor LDL receptor TG TG TG TG FFA LPL LCAT CE: cholesteryl ester FC: free cholesterol FFA: free fatty acids LCAT: lecithin cholesterol acytransferase LPL: lipoprotein lipase TG: triglycerides FFA CE CE CE FC CE Liver LDL Liver Cell in peripheral tissue VLDL Adipose tissue Adipose and other tissues HDL
    10. 10. Plasma Lipid Transport CE CE FC TG TG New synthesis LDL receptor LDL receptor TG TG TG TG FFA LPL LCAT CE: cholesteryl ester FC: free cholesterol FFA: free fatty acids LCAT: lecithin cholesterol acytransferase LPL: lipoprotein lipase TG: triglycerides FFA CE CE CE FC CE Liver LDL Liver Cell in peripheral tissue VLDL Adipose tissue Adipose and other tissues HDL
    11. 11. Plasma Lipid Transport CE CE FC TG TG New synthesis Bile LDL receptor LDL receptor TG TG TG TG FFA LPL FC LCAT CE: cholesteryl ester FC: free cholesterol FFA: free fatty acids LCAT: lecithin cholesterol acytransferase LPL: lipoprotein lipase TG: triglycerides FFA CE CE CE FC CE Liver LDL Liver Cell in peripheral tissue VLDL Adipose tissue Adipose and other tissues HDL
    12. 12. Plasma Lipid Transport CE CE FC TG TG New synthesis LDL receptor LDL receptor TG TG TG TG FFA LPL LCAT FFA CETP Bile FC CE: cholesteryl ester CETP: cholesteryl ester transfer protein FC: free cholesterol FFA: free fatty acids LCAT: lecithin cholesterol acytransferase LPL: lipoprotein lipase TG: triglycerides CE CE CE FC CE Liver LDL Liver Cell in peripheral tissue Adipose tissue VLDL Adipose and other tissues HDL
    13. 13. Dyslipidemia in Diabetes and the Metabolic Syndrome CE CE FC TG TG New synthesis CE FC LDL receptor LDL receptor CE TG TG TG TG FFA LPL LCAT FFA CETP Bile FC CE: cholesteryl ester CETP: cholesteryl ester transfer protein FC: free cholesterol FFA: free fatty acids LCAT: lecithin cholesterol acytransferase LPL: lipoprotein lipase TG: triglycerides CE CE Liver LDL Liver Cell in peripheral tissue Adipose tissue VLDL Adipose and other tissues HDL
    14. 14. Dyslipidemia in Diabetes and the Metabolic Syndrome CE CE FC TG TG New synthesis CE FC LDL receptor LDL receptor CE TG TG TG TG FFA LPL LCAT  FFA CETP Bile FC CE: cholesteryl ester CETP: cholesteryl ester transfer protein FC: free cholesterol FFA: free fatty acids LCAT: lecithin cholesterol acytransferase LPL: lipoprotein lipase TG: triglycerides CE CE Liver LDL Liver Cell in peripheral tissue Adipose tissue VLDL Adipose and other tissues HDL
    15. 15. Dyslipidemia in Diabetes and the Metabolic Syndrome CE CE FC TG TG New synthesis CE FC LDL receptor LDL receptor CE TG TG TG TG FFA LPL LCAT  FFA CETP Bile FC CE: cholesteryl ester CETP: cholesteryl ester transfer protein FC: free cholesterol FFA: free fatty acids LCAT: lecithin cholesterol acytransferase LPL: lipoprotein lipase TG: triglycerides CE CE Liver LDL Liver Cell in peripheral tissue Adipose tissue  VLDL Adipose and other tissues HDL
    16. 16. Dyslipidemia in Diabetes and the Metabolic Syndrome CE CE FC TG TG New synthesis CE FC LDL receptor LDL receptor CE TG TG TG TG FFA LCAT  LPL  FFA CETP Bile FC CE: cholesteryl ester CETP: cholesteryl ester transfer protein FC: free cholesterol FFA: free fatty acids LCAT: lecithin cholesterol acytransferase LPL: lipoprotein lipase TG: triglycerides CE CE Liver LDL Liver Cell in peripheral tissue Adipose tissue Adipose and other tissues HDL  VLDL
    17. 17. Dyslipidemia in Diabetes and the Metabolic Syndrome CE CE FC TG TG New synthesis CE FC LDL receptor LDL receptor CE TG TG TG TG FFA  LCAT  FFA  LPL CETP Bile FC CE: cholesteryl ester CETP: cholesteryl ester transfer protein FC: free cholesterol FFA: free fatty acids LCAT: lecithin cholesterol acytransferase LPL: lipoprotein lipase TG: triglycerides CE CE Liver LDL Liver Cell in peripheral tissue Adipose tissue Adipose and other tissues  HDL  VLDL
    18. 18. Dyslipidemia in Diabetes and the Metabolic Syndrome CE CE FC TG TG New synthesis CE FC LDL receptor LDL receptor CE TG TG TG TG FFA  FFA  LPL  LCAT CETP Bile FC CE: cholesteryl ester CETP: cholesteryl ester transfer protein FC: free cholesterol FFA: free fatty acids LCAT: lecithin cholesterol acytransferase LPL: lipoprotein lipase TG: triglycerides CE CE Liver LDL Liver Cell in peripheral tissue Adipose tissue Adipose and other tissues  VLDL  HDL
    19. 19. <ul><li>www.cardiometabolic-risk.org </li></ul>

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