Lipoproteins metabolism, animal studies

In humans, stress can increase the risk of cardiovascular disease by altering lipoprotein metabolism, but what about animal studies In 1988,... 

The pharmacokinetics of PFOS and PFOA have been investigated in animal studies [22-24]. Results indicate that both PFCs are well absorbed following oral exposure, and poorly eliminated. In addition, PFOS and PFOA are very persistent as they are not metabolized and undergo extensive enterohepatic circulation [25,26]. PFSAs and PFCAs are unique among other persistent halogenated organic contaminants as they do not preferentially accumulate in fatty tissues, but instead are predominately distributed in the liver, serum and kidney [22-24]. This may be explained by the fact that PFOS and PFOA bind to proteins, specifically )8-lipoproteins, albumin and liver fatty acid-binding proteins [27, 28]. 

Fernandez, M. L., and J. S. Volek. 2006. Guineapigs A suitable animal model to study lipoprotein metabolism, atherosclerosis and inflammation. Nutrition and Metabolism 3 17-23. 

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. ... 

CI-976 was synthesized as a fatty acid anilide derivative designed to mimic fatty acyl-CoA, the fatty acid donor for ACAT enzymes, and it has been most extensively studied in this regard as a competitive ACAT inhibitor (Field et al., 1991 Roth et al., 1992). Various animal studies have shown that CI-976 lowers plasma low density Upoprotein (LDL)-cholester-ol and raises high density lipoprotein-cholesterol by inhibiting both hver and intestinal ACAT activities CI-976 also lowers liver cholesterol esters (CE) and decreases CE secretion (Carr et al., 1995 Krause et al., 1993). The metabolic fate of CI-976 has been studied in both whole animals and isolated hepatocytes, and it is oxidized to numerous metabolites, likely by cytochrome P450 pathways (Sinz et al., 1997). The biological activities of these metabolites are unknown. 

It is now well established that very low density and low density lipoproteins are synthesized in the liver. Data supporting this conclusion have been obtained from studies on plasma triglyceride metabolism, the fatty liver and its origin, and protein biosynthesis in the liver. Many of the studies used animals which have a somewhat different lipoprotein pattern than the human. Metabolic sequences differ in detail between species and unique model systems are required (Farquhar et al. 1965). Nevertheless fundamental aspects of lipoprotein metabolism such as liver synthesis have been confirmed in several animals. 

The association between atherosclerosis in humans and plasma lipoproteins has led to the development and use of several animal models to help our understanding of familial hypercholesterolemias and atherosclerosis however, the species differences in lipoproteins and their metabolism must be considered when developing models of atherosclerosis and novel therapeutic agents. Dietary manipulations in animals with dominant LDL-C fractions are perhaps more appropriate models for these studies than in animals where HDL is the dominant fraction (Cayen, Givner, and Kraml... 

There are good examples from the metabolic literature of studies in which the number of data observed for a single subject is limited. An example is measuring the mean residence time of low density lipoprotein in the rabbit aortic wall (Schwenke and Carew, 1989). In experiments such as these, samples of the aorta may only be obtained once, at the end of the experiment. Thus there is only one datum for each tracer used. Schwenke and Carew (1989) used two iodine tracers, administered at different times, but the compartmental model they used has four parameters. Clearly, parameter values cannot be estimated for each animal without using information from experiments in other animals. 

It is the purpose of this review to cover recent knowledge on chemistry and metabolism of plasma lipoprotein as related to physiological and disease states. Earlier accounts on the subject can be found in the articles by Lindgren and Nichols (1960), Gurd (1960), and Oncley (1963). Most of this discussion will be concerned with lipoproteins of human plasma, which have been studied more extensively than those of other animal species. 

Discussion of fat transport in terms of lipoproteins is justified by the fact that each plasma lipid is present in blood as a constituent of lipoproteins. Unfortunately, our knowledge of lipoproteins as structural and functional units is sparse thus any attempt to give an overall view of their role in fat transport is still largely speculative. One of the most difficult problems is that of differentiating the metabolism of transported fats from metabolism of those which are structural constituents of lipoproteins, and the establishment of their interrelationship. Variations from one animal species to another are also be considered and undue generalization avoided until better comparative studies are available. 

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