Triglycerids transport

Fatty liver developed in rats fed a diet containing orotic acid is characterized by the deposition of droplets of triglycerides in the tubules of the endoplasmic reticulum [297,298]. The reticulum breaks down into individual vesicles which contain lipid droplets 0.2-0.S im in diameter which accumulate the apolipoproteins of low and very low density lipoproteins. The liver otherwise appears to be functionally normal, unlike that of animals receiving other lipotrophic agents. The administration of orotic acid has a specific effect on lipoprotein synthesis without overall inhibition of protein synthesis. The effect is selective for hepatic but not intestinal P-lipoprotein production and triglyceride transport [299]. 

Before discussing the different forms of EHL and considering some pathogenetic factors involved in the production of different syndromes, a brief summary of present understanding of triglyceride transport may be in order. No attempt will be made at this time to discuss areas of controversy. For details we refer to reviews by Fredrickson and Gordon (1958), Havel (1958), Jeanrenaud (1961), and by... 

Conventional lipid tests determine the amount of cholesterol and triglycerides transported by all particles within the lipoprotein classes or in total plasma. Thus, cholesterol and triglycerides may be regarded as surrogate markers for their carrier-lipoprotein particles. 

An overall scheme for triglyceride transport can now be visualized with roles assigned to all of the lipoprotein classes. While other functions of the plasma lipoproteins certainly exist, there is a good probability that their triglyceride transport function is a major determinant of their plasma concentrations. 

Apo-BlOO 516,000 80-100 Liver Cholesterol, triglyceride transport, receptor recognition... 

Phospholipids. Phospholipids, components of every cell membrane, are active determinants of membrane permeabiUty. They are sources of energy, components of certain enzyme systems, and involved in Hpid transport in plasma. Because of their polar nature, phosphoUpids can act as emulsifying agents (42). The stmcture of most phosphoUpids resembles that of triglycerides except that one fatty acid radical has been replaced by a radical derived from phosphoric acid and a nitrogen base, eg, choline or serine. 

Leptin is a cytokine produced and secreted by adipose tissue in proportion to the body fat content [3]. Mice and humans lacking leptin or its receptor develop a severe hyperphagia and a dramatic degree of obesity which is considerably more pronounced than that of the NDRKO mouse. Thus, leptin is the key adiposity signal in rodents and humans. Leptin secretion appears to reflect the metabolic status of the adipocyte rather than the sheer size of triglyceride deposits, and leptin levels may transiently be dissociated from total body fat. Nonetheless, over the course of a day with unrestricted food supply, plasma leptin levels reliably reflect the amount of total body fat. Local administration of leptin into the brain results in reduced food intake. The vast majority of patients with obesity have elevated serum levels of leptin. Thus, it is believed that the polygenic obesity is due to leptin resistance rather than to inadequate leptin secretion, or to a reduced blood/brain transport of the cytokine. 

Lipoprotein metabolism is the process by which hydrophobic lipids, namely triglycerides and cholesterol, are transported within the interstitial fluid and plasma. It includes the transport of energy in the form of triglycerides from intestine and liver to muscles and adipose, as well as the transport of cholesterol both from intestine and liver to peripheral tissues, as well as from peripheral tissues back to the liver. 

The main transport form of lipids in the cir culation. They are spherical macromolecules of 10-1200 nm diameter-composed of a core of neutral lipids (mostly cholesterol ester and triglycerides) surrounded by an amphipathic shell of polar phospholipids and cholesterol. Embedded in the shell of lipoproteins are apolipoproteins that are essential for assembly of theparticles in tissues that secrete lipoproteins, and for their recognition by target cells. 

This approach can be used only for fat-soluble compounds that follow the same lymphatic route to be transported to the liver as carotenoids. The bioavailability of the compound of interest is determined by monitoring the appearance of the compound and its newly formed intestinal metabolites in the postprandial chylomicron fraction of plasma [also called the density < 1.006 kg/L fraction or triglyceride-rich lipoprotein (TRL) fraction because it is generally a mixture of chylomicrons (CMs) and very low density lipoproteins (VLDLs)] as a function of the time after ingestion. 

In this in vitro system, the presence of serum in cell culture medium is not necessary, but the type of transwell is important (the total amount of H-triglycerides secreted was two-fold higher when using 3 pm versus 1 pm pore size transwells), and oleic acid supplementation is required for the formation and secretion of CMs as well as the transport of 3-carotene through Caco-2 cells. Finally, the presence of Tween 40 does not affect CM synthesis and secretion in this in vitro cell culture system. Thus, CMs secreted by Caco-2 cells were characterized as particles rich in newly synthesized H-triglycerides (90% of total secreted) containing apolipoprotein B (30% of total secreted) and H-phospholipids (20% of total secreted) and with an average diameter of 60 nm. These characteristics are close to those of CMs secreted in vivo by enterocytes. ... 

Niacin (vitamin B3) has broad applications in the treatment of lipid disorders when used at higher doses than those used as a nutritional supplement. Niacin inhibits fatty acid release from adipose tissue and inhibits fatty acid and triglyceride production in liver cells. This results in an increased intracellular degradation of apolipoprotein B, and in turn, a reduction in the number of VLDL particles secreted (Fig. 9-4). The lower VLDL levels and the lower triglyceride content in these particles leads to an overall reduction in LDL cholesterol as well as a decrease in the number of small, dense LDL particles. Niacin also reduces the uptake of HDL-apolipoprotein A1 particles and increases uptake of cholesterol esters by the liver, thus improving the efficiency of reverse cholesterol transport between HDL particles and vascular tissue (Fig. 9-4). Niacin is indicated for patients with elevated triglycerides, low HDL cholesterol, and elevated LDL cholesterol.3... 

Hepatic steatosis usually is a result of excessive administration of carbohydrates and/or lipids, but deficiencies of carnitine, choline, and essential fatty acids also may contribute. Hepatic steatosis can be minimized or reversed by avoiding overfeeding, especially from dextrose and lipids.35,38 Carnitine is an important amine that transports long-chain triglycerides into the mitochondria for oxidation, but carnitine deficiency in adults is extremely rare and is mostly a problem in premature infants and patients receiving chronic dialysis. Choline is an essential amine required for synthesis of cell membrane components such as phospholipids. Although a true choline deficiency is rare, preliminary studies of choline supplementation to adult patients PN caused reversal of steatosis. 

Lipoproteins. A lipoprotein is an endogenous macromolecule consisting of an inner apolar core of cholesteryl esters and triglycerides surrounded by a monolayer of phospholipid embedded with cholesterol and apoproteins. The functions of lipoproteins are to transport lipids and to mediate lipid metabolism. There are four main types of lipoproteins (classified based on their flotation rates in salt solutions) chylomicrons, very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). These differ in size, molecular weight, and density and have different lipid, protein, and apoprotein compositions (Table 11). The apoproteins are important determinants in the metabolism of lipoproteins—they serve as ligands for lipoprotein receptors and as mediators in lipoproteins interconversion by enzymes. 

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