Effect of infant diets with different polyunsaturated to saturated fat ratios on circulating high-density lipoproteins.
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Biomedical subjects
Publications and source records attributed to S E Carlson.
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Intact, but sham-operated female rats had 2- to 3-fold higher levels of hepatic 3-hydroxy-3-methylglutaryl CoA reductase activity than their male counterparts (15--21.5 vs. 6.7--8.7 nmol mevalonate/mg protein per h). The activity of the hepatic enzyme declined to about the same relative degree (40--60%) in male and female rats that were gonadectomized after puberty (53 days of age) and killed 5 weeks later. Implantation of silastic capsules containing 17 beta-estradiol increased the level of hepatic 3-hydroxy-3-methylglutaryl CoA reductase to levels found in sham-operated controls. In rats that were gonadectomized in infancy (12 h old) and killed 7--8 weeks later, the level of enzyme activity was not altered in females, but it was increased from 60--240% in males. Consequently, following neonatal gonadectomy, male-female differences in enzyme activity were no longer apparent. Implantation of silastic capsules containing estradiol in neonatally gonadectomized rats resulted in a doubling of enzyme activity in both males and females. Ovariectomy reduced plasma estrogen levels, but implantation of estradiol in gonadectomized males and females increased the hormone level to that found in sham-operated females. Thus, the results strongly suggest a role for physiologic levels of estrogen as a positive effector of 3-hydroxy-3-methylglutaryl CoA reductase activity. Neonatal sex imprinting also appears to modulate the enzyme activity since sex-mediated differences are effaced by gonadectomy in infancy, but not by gonadectomy following puberty.
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The activities of hepatic microsomal 3-hydroxy-3-methylglutaryl CoA reductase and cholesterol 7alpha-hydroxylase were consistently higher (up to 3-fold) in female compared to male rats fed 2% cholestyramine for 8 h daily. In all animals studied, enzymic activities were highest 6 h after feeding began. However, 85% of the rise in cholesterol 7alpha-hydroxylase activity occurred in the 6 h before and 89% of the rise in 3-hydroxy-3-methylglutaryl CoA reductase activity occurred in the 6 h after feeding started. Sex-related differences in both enzymic activities first became apparent at the time of sexual maturity. Enzymic activities before weaning were generally low and a late-suckling (13--20 days) rise in cholesterol 7alpha-hydroxylase was not accompanied by a rise in 3-hydroxy-3-methylglutaryl CoA reductase. For all of these studies we assayed cholesterol 7alpha-hydroxylase at two concentrations of exogenous cholesterol to obviate problems relating to size of the cholesterol pool.
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An experimental model in which adult rats underwent rapid rates of tissue repletion after dietary restriction served to explore the influence of dietary fat on cholesterol metabolism. Adult rats severely restricted in protein and energy were refed either 8 or 24 hours per day for 10 days. Refeeding diets contained approximately 0% or 20% fat by weight as safflower oil or beef tallow and 4% or 17% protein on an energy basis. Concentration or source of dietary fat did not significantly influence either serum or hepatic cholesterol concentrations. Inclusion of dietary fat increased incorporation of 3H-acetate into digitonin precipitable sterols although type of fat did not influence this parameter. Specific activities of serum and hepatic cholesterol were identical for rats fed with diets containing safflower oil and beef tallow, but an elevation in acidic 14C-steroid excretion per g diet consumed occurred with safflower oil as compared with beef tallow. The data suggest that, in the absence of exogenous cholesterol, high levels of polyunsaturated fat may influence cholesterol metabolism primarily by increasing synthesis and excretion of bile acids.
An enzymatic assay currently in use in clinical laboratories for quantitating total serum cholesterol has been modified for the determination of microgram quantities of tissue cholesterol. Two types of assays were developed. In the first, more generally useful method, lipids extracted with chloroform/methanol were solubilized by the addition of detergent and assayed for free and total cholesterol using laboratory prepared mixtures of reagents. Although different detergents were effective, it appears that Triton X-100 may be most universally applicable. In the second type of assay, commercially available reagent mixtures were employed for the determination of total cholesterol only. Results of both types of assays compare favorably with determination using the colorimetric assay on 3beta-hydroxysterols recovered from digitonides.
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