Very low-density lipoproteins secretion

V.A.Kosykh, V.Z.Lankin, E.A.Podrez, D.K.Novikov, S.A.Volgushev, A.V.Victorov, V.S.Repin and V.N. Smirnov, Very low density lipoprotein secretion by cultured hepatocytes of rabbits fed purified or autoxidized cholesterol. Lipids 24 (1989) 109-115. 

VLDL Very low-density lipoproteins secreted by the liver the initial transporter of cholesterol and other lipids from the liver to the periphery... 

Bartlett, S.M. Gibbons, G.F. (1988) Biochem. J., 249, 37-43. Short- and longer-term regulation of very-low-density lipoprotein secretion by insulin, dexamethasone and lipogenic substrates in cultured hepatocytes. 

Liver secretion of very low density lipoproteins contributed to the daily turnover of plasma RRR-a-tocopherol. Patients with the autosomal recessive neurodegenerative disease called ataxia with isolated vitamin E deficiency have an impaired ability to incorporate a-tocopherol into very low density lipoproteins secreted by the liver, because of mutations in the gene encoding the tocopherol transfer protein. 

The effects of colchicine on RBP secretion and metabolism by the liver were explored by Smith et al. (1980). Colchicine treatment of retinol-deficient rats markedly inhibited the retinol-stimulated secretion of RBP from the liver into the serum. The inhibition of RBP secretion was quantitatively quite similar to the inhibition of very low-density lipoprotein secretion by colchicine seen in parallel experiments. In contrast, colchicine did not affect the overall rate of protein synthesis within the liver. The inhibition of RBP secretion by colchicine suggests that the microtubules play a role in RBP secretion. 

Acyl-CoA cholesterol acyl transferase (ACAT) catalyzes the intracellular formation of cholesteryl esters (CE) in all mammalian cells. It has been implicated as a key enzyme involved in cholesterol absorption, very low density lipoprotein secretion, and the formation of lipid-laden macrophages. The accumulation of CE in macrophage-derived foam cells is characteristic of the early step in the development of atherosclerosis. ACAT inhibitors reduced TC levels without affecting HDL-C. This can be attributed to decreased intestinal cholesterol absorption based on binding to bile acid (Turley SD. and Herndon MW. 1994)... 

Figure 25-2. The formation and secretion of (A) chylomicrons by an intestinal cell and (B) very low density lipoproteins by a hepatic cell. (RER, rough endoplasmic reticulum SER, smooth endoplasmic reticulum G, Golgi apparatus N, nucleus C, chylomicrons VLDL, very low density lipoproteins E, endothelium SD, space of Disse, containing blood plasma.) Apolipoprotein B, synthesized in the RER, is incorporated into lipoproteins in the SER, the main site of synthesis of triacylglycerol. After addition of carbohydrate residues in G, they are released from the cell by reverse pinocytosis. Chylomicrons pass into the lymphatic system. VLDL are secreted into the space of Disse and then into the hepatic sinusoids through fenestrae in the endothelial lining.

Shelness GS, Sellers JA Very-low-density lipoprotein assembly and secretion. Curr Opin Lipidol 2001 12 151. 

In the enterocyte, provitamin A carotenoids are immediately converted to vitamin A esters. Carotenoids, vitamin A esters, and other lipophilic compounds are packaged into chylomicrons, which are secreted into lymph and then into the bloodstream. Chylomicrons are attacked by endothelial lipoprotein lipases in the bloodstream, leading to chylomicron remnants, which are taken up by the liver (van den Berg and others 2000). Carotenoids are exported from liver to various tissues by lipoproteins. Carotenes (such as (3-carotene and lycopene) are transported by low-density lipoproteins (LDL) and very low-density lipoproteins (VLDL), whereas xanthophylls (such as lutein, zeax-anthin, and (3-cryptoxanthin) are transported by high-density lipoproteins (HDL) and LDL (Furr and Clark 1997). 

Very low density lipoprotein is not the only lipoprotein to be secreted by the liver. HDL is released into the blood as a nascent (immature) discoid particle. As the HDL circulates within the circulation, it matures by exchanging apoproteins and lipid components with other lipoproteins and cells. Mature spherical HDL is... 

The resulting triacylglycerol is stored in adipose tissue. In the liver, some is combined with protein and phospholipids to form a complex, known as very low density lipoprotein (VLDL), which is secreted from the liver into the blood. Details of the formation of VLDL are presented in Appendix 11.2. Failure to form VLDL or secrete can cause accu-... 

Increased secretion and decreased catabolism of very low density lipoprotein. Arterioscler Thromb 1991 CN115... 

Secretion of nonglycosylated macromolecules in the presence of tunicamycin has also been investigated in a number of other cells. Rat-liver cell-secretion ol albumin (a carbohydrate-free protein), transferrin, and a-acid glycoprotein was not inhibited, and, in chick-liver cells, only a decrease by 10-25% in the secretion of transferrin and the apoprotein B chain of very-low-density lipoprotein was noted.463,464 The secretion of ovalbumin (a glycoprotein) from hen oviduct was not blocked by tunicamycin.465... 

Fig. 5.2.1 The major metabolic pathways of the lipoprotein metabolism are shown. Chylomicrons (Chylo) are secreted from the intestine and are metabolized by lipoprotein lipase (LPL) before the remnants are taken up by the liver. The liver secretes very-low-density lipoproteins (VLDL) to distribute lipids to the periphery. These VLDL are hydrolyzed by LPL and hepatic lipase (HL) to result in intermediate-density lipoproteins (IDL) and low-density lipoproteins (LDL), respectively, which then is cleared from the blood by the LDL receptor (LDLR). The liver and the intestine secrete apolipoprotein AI, which forms pre-jS-high-density lipoproteins (pre-jl-HDL) in blood. These pre-/ -HDL accept phospholipids and cholesterol from hepatic and peripheral cells through the activity of the ATP binding cassette transporter Al. Subsequent cholesterol esterification by lecithinxholesterol acyltransferase (LCAT) and transfer of phospholipids by phospholipid transfer protein (PLTP) transform the nascent discoidal high-density lipoproteins (HDL disc) into a spherical particle and increase the size to HDL2. For the elimination of cholesterol from HDL, two possible pathways exist (1) direct hepatic uptake of lipids through scavenger receptor B1 (SR-BI) and HL, and (2) cholesteryl ester transfer protein (CfiTP)-mediated transfer of cholesterol-esters from HDL2 to chylomicrons, and VLDL and hepatic uptake of the lipids via the LDLR pathway...

In adipose tissue, TAG is stored in the cytosol of the cells in a nearly anhydrous form. It serves as "depot fat," ready for mobilization when the body requires it for fuel. Little TAG is stored in the liver. Instead, most is exported, packaged with cholesteryl esters, cholesterol, phospholipid, and protein (apolipoprotein B-100, see p. 229) to form lipoprotein particles called very low density lipoproteins (VLDL). Nascent VLDL are secreted into the blood where they mature and function to deliver the endogenously-derived lipids to the peripheral tissues. [Note Recall that chylomicrons deliver primarily dietary (exogenously-derived) lipids.] Plasma lipoproteins are discussed in Chapter 18, p. 225. 

I Liver secretes nascent TG-rich very-low-density lipoprotein particles. 

Synthesis of lipids from carbohydrates is an efficient process, which occurs largely in the liver and also in intestinal epithelial cells.6 The newly synthesized triacylglycerols, together with smaller amounts of phospholipids and cholesterol, combine with specific apolipoproteins, which are also synthesized in the liver, to form very low density lipoprotein (VLDL) particles which are secreted into the blood stream. 

Davis, R., Lipoprotein structure and secretion. In D. E. Vance, and J. E. Vance (eds.), Biochemistry of Lipids, Lipoproteins and Membranes. Amsterdam Elsevier Science Publishers, 1991. This chapter (14) provides an advanced discussion on the assembly and secretion of very-low-density lipoproteins. 

Fatty liver refers to the abnormal accumulation of fat in hepatocytes. At the same time there is a decrease in plasma lipids and lipoproteins. Although many toxicants may cause lipid accumulation in the liver (Table 14.1), the mechanisms may be different. Basically lipid accumulation is related to disturbances in either the synthesis or the secretion of lipoproteins. Excess lipid can result from an oversupply of free fatty acids from adipose tissues or, more commonly, from impaired release of triglycerides from the liver into the plasma. Triglycerides are secreted from the liver as lipoproteins (very low density lipoprotein, VLDL). As might be expected, there are a number of points at which this process can be disrupted. Some of the more important ones are as follows (Figure 14.1) ... 

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