Lipoprotein lipase gene expression

Another interesting innovation is the registration of alipogene tiparvovec, it represents the first gene therapy treatment that has reached the market [15]. The medicinal product consists of the human lipoprotein lipase gene that is encapsulated in a vector derived from adeno-associated vims (AAV), serotype 1. The viral vector will deliver the gene into the cell, in this case a muscle cell, where the gene can be expressed after which the lipoprotein lipase is produced, fii... 

Both PL and LPL require cofactors for full expression of activity (CLP and apoC-11, respectively) no such cofactor is necessary for HL. Derewenda and Cambillau (1991) postulated that, in the human lipase gene family of enzymes, the loops of the N-terminal domain, which exhibit the most pronounced variation in their amino acid sequences, may be responsible for conferring specificity with respect to cofactors. The structure of the lipase-procolipase complex (van Tilbeurgh et al., 1992 see above) does not support this hypothesis. However, in the case of LPL the structural basis of its interaction with apoC-11 may be quite different. Wong et al. (1991) and Davis et al. (1992) produced hybrid molecules by interchanging the C-terminal domains between the rat hepatic and lipoprotein lipases. Their HL chimera, made up of the HL N-terminal catalytic domain and the LPL C-terminal fragment, exhibited the salt-resistant catalydc properties characteristic of HL, but was... 

IDL) to LDL, and probably also by maintaining lipoprotein lipase activity which promotes triglyceride clearance. In liver, kidney, skeletal muscle, cardiac muscle, and adipose tissue, thyroid hormone stimulates Na", K+-ATPase gene expression and promotes thermogenesis. 

BAT, in its cold/epinephrine-activated state compared to an atrophied or quiescent state, demonstrates increases in blood flow, lipoprotein lipase activity, triacylglycerol synthesis, 5 -deiodinase activity, and triiodothyronine-enhanced UCP gene expression. The processes of fatty acid uptake and triacylglycerol synthesis are essentially the same in both BAT and WAT. However, norepinephrine release by the sympathetic nervous system in acute cold exposure stimulates BAT to enhance expression and secretion of lipoprotein lipase to its sites in the vascular epithelium. Lipoprotein lipase releases fatty acids from passing chylomicrons and very low-density lipoproteins (Chapter 20), causing an influx of fatty acids into the brown adipocytes. 

Several lines of evidence have implicated apolipoprotein (apo) C-III in plasma TG metabolism. Reports have indicated that apo C-III inhibits TG hydrolysis by LPL and hepatic lipase in vitro and impairs the uptake of TG-rieh lipoproteins hy the liver. Moreover, transgenic animal studies, in whieh the plasma TG levels are proportional to plasma apo C-III concentrations and liver apo C-III gene expression, provided more direct evidence for the causal involvement of apo C-III in h5 ertriglyeeridemia. Recently, it has been shown that fibrate downregulates apo C-III e qiression (Table 1) and this may contribute for the hypotriglyceridemic action of these drugs. ... 

Ringseis, R., C. Dathe, A. Muschick, C. Brandsch, and K. Eder. 2007c. Oxidized fat reduces milk triacylglycerol concentrations by inhibiting gene expression of lipoprotein lipase and fatty acid transporters in the mammary gland of rats./oM/TJoZ ofJVMtriiion 137 2056-2061. 

The underlying causes are either the absence of a specific enzyme (e.g. lipoprotein lipase in Type I) the absence of a specific apolipoprotein (e.g. apoC2 in another form of Type I) the absence, reduction or impairment of function of specific cell surface receptors (e.g. the LDL receptor in Type Ila) the overproduction of specific apolipoproteins (e.g. apoB in Type Ilb) or the overproduction of lipids in the liver (e.g. triacylglycerols in Types IV and V). Different gene defects may produce the same lipoprotein pattern although by different mechanisms. Alternatively, factors such as body weight and dietary composition may modify the phenotypic expression of a particular genotype. 

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