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Triglyceride (TG), a water-insoluble energy-rich lipid, is secreted by the liver as part of very low density lipoproteins (VLDLs) to supply energy to extrahepatic tissues. Overproduction of VLDL is associated with increased risk of cardiovascular heart disease; this has renewed an interest in factors that affect hepatic TG production. The TG production rate is determined by measuring temporal increases in plasma TG under conditions in which TG hydrolysis by lipoprotein lipase (LPL) is inhibited. The nonionic detergent, Triton WR-1339 (Triton), has commonly been used to inhibit LPL for this purpose. Triton, in addition to inhibition of TG hydrolysis, has properties that have the potential to adversely influence lipoprotein metabolism. Another nonionic detergent, poloxamer 407 (P-407), also inhibits LPL. In these studies, we demonstrate that P-407 is comparable to Triton in the determination of TG production but without the unwanted side effects of Triton. Supplementary key words non-ionic detergents • hepatic lipids • lipoproteinsTriglyceride (TG) is an energy-rich compound, primarily stored in liver and adipose, and is mobilized in response to various metabolic signals. In plasma, TG, which is water insoluble, circulates as the neutral lipid core of lipoproteins, mainly chylomicrons, which carry dietary fat and are secreted by the small intestine, and very low density lipoproteins (VLDLs), which carry TG from the liver. Overproduction of VLDL has been associated with a number of disease states that result in an increased risk of cardiovascular heart disease; this has renewed an interest in factors that affect hepatic TG (lipoprotein) production (1).In the early 1950s, it was noted that intravenous injection of certain nonionic detergents resulted in milky serum that lasted up to 48 h (2). This was later shown to be due to the inhibition of TG hydrolysis by lipoprotein lipase (LPL) (3). Since then, lipolysis inhibition has been used to determine hepatic TG production rates, with Triton WR-1339 (also known as Tyloxapol) being widely used. Using this technique, the TG production rate is calculated from the increase in TG over time following detergent injection. Although this method is the basis for most studies on TG production in animals, there is considerable variation in its implementation. Variables include whether mice are fasted, fed chow or a fat-free diet, and what the plasma sampling period is (0 to 300 min) over which TG production rates are determined ( Table 1 ).In addition to inhibition of LPL, Triton has a number of other physiologic effects related to lipoprotein metabolism. Triton has been shown to cause dissociation of apolipoprotein A-I (apoA-I) and apoC-II from HDL (13). Triton is rapidly taken up by the liver, where it accumulates in the lysosomes, causes autophagic vacuole formation (14, 15), and is excreted in bile, possibly explaining a reduction in biliary phospholipid and cholesterol output (16). These hepatic and plasma effects of Triton may affect hepatic TG production, especial...
Background-Factors that regulate the metabolism of HDL and apolipoprotein A-I (apoA-I) are incompletely understood.Overexpression of endothelial lipase (EL) markedly reduces plasma levels of HDL cholesterol and apoA-I in mice, but the mechanisms of this effect remain unknown. Methods and Results-We used different doses of a recombinant adenoviral vector to overexpress human EL in mice and studied the effects on plasma phospholipase activity, plasma lipids, HDL particle size, HDL turnover, and tissue sites of HDL degradation in mice. Overexpression of EL was associated with a significant dose-dependent increase in postheparin plasma phospholipase activity. Plasma phospholipid, HDL cholesterol, and apoA-I levels were markedly decreased, even at the lowest dose of vector. Kinetic studies demonstrated a significant dose-dependent increase in the fractional catabolic rate of HDL-apolipoprotein in EL-overexpressing mice. The postheparin plasma phospholipase activity was significantly positively correlated with HDL-apolipoprotein fractional catabolic rate. The uptake of apoA-I by the kidney and the liver was significantly increased by 2.5-fold and 3-fold, respectively, in mice overexpressing EL. Conclusions-Expression
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