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D K Spady

Publications and source records attributed to D K Spady.

56 records · Page 4Linked to original sources
PubMed1983

Sterol synthesis in vivo in 18 tissues of the squirrel monkey, guinea pig, rabbit, hamster, and rat.

This study was undertaken to measure and compare the rates at which digitonin-precipitable sterols (DPS) were synthesized in vivo in the major organs of five different animal species. These rates were assessed by measuring the velocity at which [3H]water was incorporated into DPS in the intact animal. The animals used were chosen to include species that carried most of their plasma cholesterol either predominantly in high (rat, hamster) or low (guinea pig) density lipoproteins (HDL and LDL, respectively) or more evenly distributed between the LDL and HDL fractions (monkey and rabbit). Whole animal sterol synthesis was much higher in the rat (16.1 mumol/hr) than in the other four species (2.9-4.6 mumol/hr) when normalized to a constant body weight of 100 g. This uniquely high rate of sterol synthesis could be attributed predominantly to an extremely high rate of incorporation of [3H]water into DPS by the liver of the rat. When expressed per g of tissue, the highest content of newly synthesized sterol in all species was found in tissues such as adrenal gland, ovary, and gastrointestinal tract. However, the content of [3H]DPS in the liver varied markedly from a high of 2279 nmol/hr per g in the rat to a low of only 109 nmol/hr per g in the guinea pig. Consequently, when expressed as a percentage of total body synthesis, the whole liver of the rat contained 51% of the [3H]DPS while this figure was much lower in the monkey (40%), hamster (27%), rabbit (18%), and guinea pig (16%). Thus, in all species except the rat, the major sites for sterol synthesis appeared to be the gastrointestinal tract, carcass (predominantly the muscle), and skin. In addition, even though the content of newly synthesized sterol per g of adrenal gland was higher than in nearly any other tissue in all of the species examined, it was further demonstrated that in the rat most of this [3H]DPS was derived from the blood (and, therefore, ultimately from the liver) whereas in the other species it was largely synthesized locally within the gland. Thus, these studies demonstrated that in many species the liver is quantitatively far less important as a site for sterol synthesis than previously believed and, as a correlate of this, most sterol utilized by extrahepatic tissues is largely synthesized locally within those tissues.

Animals↗
PubMed1983

Alteration of the degree of biliary cholesterol saturation in the hamster and rat by manipulation of the pools of preformed and newly synthesized cholesterol.

Our studies compared the effects of changing the availability of newly synthesized and preformed cholesterol by various dietary manipulations on biliary cholesterol secretion in the hamster and rat. In hamsters fed a plain pelleted diet, only 2%-5% of biliary cholesterol was derived directly from newly synthesized sterol. Cholestyramine feeding, through a stimulation of hepatic sterol synthesis, increased this fraction fivefold but did not change total biliary cholesterol output. The relative cholesterol content increased significantly due to a reduction in bile acid and phospholipid output. In contrast, biliary cholesterol output was increased several-fold in hamsters fed a fat-free diet. These animals also manifested a pronounced increase in whole-body sterol synthesis, this being due principally to an increase in hepatic sterol synthesis. Although this resulted in the transport of much more newly synthesized cholesterol directly into bile, this did not account for the disproportionately high rate of biliary cholesterol output. Such excess sterol was derived predominantly from a preformed source. Unlike hamsters, rats fed the fat-free diet manifested a marked reduction in hepatic and whole-body sterol synthesis, bile acid pool size, and bile acid and cholesterol output in bile. These studies demonstrate that when hepatic cholesterol synthesis increases in response to a need for more sterol in the body, a greater proportion of biliary cholesterol is derived directly from newly synthesized sterol, but total biliary cholesterol output is unchanged. In contrast, when more cholesterol is synthesized than is needed to maintain cholesterol balance, biliary cholesterol output may increase. Such excess biliary sterol is derived predominantly from a preformed source rather than from the transport of newly synthesized sterol directly across the canalicular membrane.

Animals↗