The Concept of CMR

Intravascular transport of dietary fat

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Figure 7: Chylomicron metabolism: the fate of dietary fat

Figure 7: Chylomicron metabolism: the fate of dietary fat

Dietary fat, which is mainly composed of phospholipids (not addressed here), triglycerides, and cholesterol, is taken up by the intestinal cells. Though the gut is very efficient at absorbing triglycerides (close to 100%), it is less efficient at absorbing cholesterol and absorption can range from 1/3 to 2/3 of the amount ingested. Some drugs interfere with intestinal cholesterol absorption and play a role in lowering blood cholesterol levels. Once absorbed by the intestinal cells, dietary lipids are packaged into lipid-rich lipoproteins known as chylomicrons through a process resembling that of VLDL synthesis in the liver (10). Chylomicrons differ from VLDL in that their major apolipoprotein is apo B48 instead of B100 and their lipid content is much greater than the liver-derived particles. Once in the bloodstream, chylomicrons are acted upon by the enzyme LPL (exactly as VLDL), which hydrolyzes the triglyceride moiety of chylomicrons to produce fatty acids that are then taken up by the various tissues sensitive to LPL action (Figure 7). The resulting particle, the chylomicron remnant, is thus depleted of triglycerides and relatively richer in cholesterol. It has become small enough to leave the blood capillaries and come into contact with a receptor, LDL-related protein (LRP), located on the surface of liver cells. The chylomicron remnant is then internalized and degraded, delivering to the liver its load of dietary cholesterol.

The basic processes of fasting lipoprotein metabolism continue in the postprandial state. However, in healthy people, several adaptations take place upon food ingestion, mainly to reduce the output of endogenous lipids into the circulation and route dietary lipids to the appropriate tissues. Insulin plays a key role in these adaptations. As seen above, insulin tends to reduce VLDL secretion. This is amplified by the postprandial rise in insulin. After a meal, the liver therefore puts out fewer triglycerides, making LPL more available for hydrolysis of chylomicron-bound dietary triglycerides. The postprandial rise in insulin also strongly amplifies the hormone’s lipolysis-inhibiting action in adipose tissue, which greatly reduces the release of fatty acids into the bloodstream. In addition, higher insulin levels switch LPL activity, which increases in adipose tissue at the expense of muscle tissue to favour storage of the incoming chylomicron-bound dietary fat (6, 11-13).

Reference

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6. Olivecrona T, Hultin M, Bergo M, et al. Lipoprotein lipase: regulation and role in lipoprotein metabolism. Proc Nutr Soc 1997; 56: 723-9.

10. Hussain MM, Fatma S, Pan X, et al. Intestinal lipoprotein assembly. Curr Opin Lipidol 2005; 16: 281-5.

11. Taskinen MR. Diabetic dyslipidaemia: from basic research to clinical practice. Diabetologia 2003; 46: 733-49.

12. Taskinen MR. Type 2 diabetes as a lipid disorder. Curr Mol Med 2005; 5: 297-308.

13. Yki-Jarvinen H. Fat in the liver and insulin resistance. Ann Med 2005; 37: 347-56.

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