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Biomedical subjects

G E Mott

Publications and source records attributed to G E Mott.

At least 73 records · Page 4Linked to original sources

Diet and sire effects on serum cholesterol and cholesterol absorption in infant baboons (Papio cynocephalus).

One hundred three baboon infants, the progeny of an equal number of dams and seven sires, were breast fed or were fed prepared formulas containing 1.2, 29, or 61 mg/dl cholesterol for 14 weeks. We measured serum cholesterol and triglyceride concentrations at birth and at 3-week intervals, and cholesterol absorption at 12 weeks. Dietary cholesterol had a significant effect on serum cholesterol concentration at 12 weeks and on cholesterol absorption, but did not affect weight or serum triglyceride concentration. Sire had a significant effect on serum cholesterol concentration at birth and at 12 weeks, but the effect at birth did not predict the effect at 12 weeks. Sire did not affect cholesterol absorption, serum triglyceride concentration, or weight at 12 weeks. The sire effect on serum cholesterol concentration in infancy is not mediated by control of cholesterol absorption. Males weighed more than females at 12 weeks, but sex did not affect serum cholesterol concentration, triglyceride concentration, or cholesterol absorption.

Age Factors↗

Estrogens and experimental atherosclerosis in the baboon (Papio cynocephalus).

One hundred twenty-six adult female baboons (Papio cynocephalus) were hysterectomized and all except 18 were ovariectomized. The animals were fed a moderately atherogenic diet (40% calories form hydrogenated vegetable oil, 1.5 gm cholesterol/kcal) for two years. Ovariectomized-hysterectomized animals received estrone sulfate, ethynyl estradiol, or diethylstilbestrol orally in daily doses similar to those given humans. An ovariectomized-hysterectomized group and a hysterectomized group received no drug. The average total serum cholesterol concentration rose from 136 mg/dl to 223 mg/dl and declined to 186 mg/dl. Concentrations of cholesterol, triglyceride, and phospholipid in whole serum, low density lipoproteins and high density lipoproteins showed no consistent statistically significant differences among the groups. Triglyceride and phospholipid concentrations were higher in the estrogen-treated and intact-ovary groups than in the ovariectomized nonestrogen treated group, but not all pairwise comparisons were statistically significant. There were no consistent statistically significant differences in atherosclerotic lesions among the groups. Neither ovariectomy nor estrogen replacement influence diet-induced experimental atherosclerosis in the baboon within two years.

Animals↗

Gas-liquid chromatography of hyocholic acid.

Partial derivatives of hyocholic acid were formed under the usual conditions for trifluoroacetylation of bile acids (trifluoroacetic anhydride, 35 degrees C for 20 min). Complete trifluoroacetylation of hyocholic acid was achieved at 80 degrees C for 30 min, or at 60 degrees C for 30 min when a trace of pyridine was added to the reaction mixture.

Bile Acids and Salts↗

Genetic effects on serum cholesterol concentrations in baboons.

Six male and 134 female adult baboons were assigned to high or low lines on the basis of response of total serum cholesterol concentration to a high cholesterol, high saturated fat diet. Positive assortative mating of these breeders produced 36 high-line and 42 low-line progeny, of which 30 high-line and 39 low-line progeny survived to one year of age. The mean serum cholesterol concentrations of the progeny produced in the two lines were significantly different at all ages from birth to one year. The serum cholesterol levels at birth were not strongly correlated with subsequent levels, but those after 3 weeks were highly correlated with one another. Heritability of total serum cholesterol concentration was estimated by realized heritability, correlation coefficients between parent and progeny values, and by regression coefficients of progeny values on mid-parent value. Estimates of heritability of serum cholesterol level at birth were low, but from 3 weeks to one year of age they ranged from 0.25 to 0.80 and averaged about 0.45. There was a correlated response of HDL and LDL cholesterol levels at one year to selection for total serum cholesterol.

Animals↗

Relationship of lipoprotein cholesterol concentrations to experimental atherosclerosis in baboons.

For 26 months, we fed baboons a high saturated fat, high cholesterol diet that contained very low concentrations of four common pesticides (chlordane, parathion, diazinon, and carbofuran). We detected no effect of pesticides on body weight, serum lipid, or lipoprotein cholesterol concentrations, or experimental atherosclerosis. We then examined the associations of serum lipid and lipoprotein cholesterol concentrations (predictor variables) with arterial lesions (response variables). Among predictor variables, very low density lipoprotein plus low density lipoprotein cholesterol concentration showed a positive association with fatty streaks in the aorta and its major branches, including the coronary arteries, while high density lipoprotein cholesterol concentration showed a consistently negative association. The very low density lipoprotein plus low density lipoprotein/high density lipoprotein cholesterol ratio was more highly associated with lesions than was either value alone. These results are consistent with epidemiologic evidence suggesting that high density lipoprotein cholesterol concentration is inversely related to probability of developing clinically manifest atherosclerotic disease.

Animals↗

Responses of serum lipoproteins to dietary cholesterol and type of fat in the baboon.

We examined the effects of dietary cholesterol (less than 0.01 and 1.7 mg/Kcal) and type of fat (saturated, coconut oil; polysaturated, corn oil) on very low density plus low density lipoprotein (VLDL + LDL) and high density lipoprotein (HDL) cholesterol in 24 young baboons (12 male, 12 female) Paplo sp.) in a crossover design experiment. The oils contributed 40% of calories. Total serum cholesterol concentration on the low cholesterol-polyunsaturated fat diet averaged 120 mg/dl; on the high cholesterol-saturated fat diet, 245 mg/dl; and on the other two cholesterol-fat diet combinations, about 200 mg/dl. There was a significant interaction between cholesterol and type of fat in their effects on VLDL + LDL cholesterol, but not in their effects on HDL cholesterol. Dietary cholesterol elevated VLDL + LDL cholesterol when fed with both types of fat, but elevated it more when fed with polyunsaturated fat than with saturated fat. Saturated fat elevated VLDL + LDL cholesterol when dietary cholesterol was low, but not when dietary cholesterol was high. Saturated fat consistently elevated HDL cholesterol more than did dietary cholesterol. The response of apolipoprotein B concentrations to dietary components was similar to that of VLDL + LDL cholesterol. These results indicate that dietary cholesterol and type of fat have different effects on the distribution of cholesterol among the major serum lipoproteins of the baboon.

Animals↗

Cholesterol metabolism in juvenile baboons. Influence of infant and juvenile diets.

The deferred effects of infant diets and the effects of juvenile diets on cholesterol metabolism were estimated in 83 baboons (Papio sp.) at 3.5 years of age. As infants, the animals were breast-fed or fed one of three formulas containing approximately 2, 30, or 60 mg/dl cholesterol. After weaning at 14 weeks of age, the animals were fed one of four juvenile diets high or low in cholesterol with saturated (P/S = 0.37) or unsaturated (P/S = 2.1) fats. Cholesterol absorption and cholesterol turnover were measured by fecal isotopic methods, and variables of cholesterol metabolism were estimated from a two-pool model. Among juvenile animals breast-fed during infancy, the percentage of cholesterol absorption was higher, while the fluxes of cholesterol from Pool A (QAA, QA, and QAB) and the cholesterol mass of Pool B were lower, compared to those fed formulas. The level of cholesterol in formulas fed during infancy did not influence cholesterol metabolism during the juvenile period. During the juvenile period, saturated fat significantly decreased the cholesterol production rate (QA) and increased the rate constants for cholesterol flux between Pool A and Pool B (KAB and KBA) compared to unsaturated fat. High cholesterol intake increased bile acid and neutral steroid excretion, cholesterol turnover rate, the mass of Pool A, and the rate constant KA and fluxes QA and QAA for removal of cholesterol from Pool A. However, KAB, t1/2 B (half-time of Pool B), and the percentage of cholesterol absorbed were decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of two forms of hypertension on atherosclerosis in the hyperlipidemic baboon.

We examined the relationship of hypertension and plasma renin activity to atherogenesis in 48 moderately hyperlipidemic (total serum cholesterol was about 200 mg/dl) baboons (Papio sp.). We used renal artery stenosis (two-kidney, one clip model) to produce hypertension associated with elevated plasma renin activity, and used cellophane wrapping of both kidneys (bilateral perinephritis model) to produce hypertension with normal renin activity. Renal artery stenosis and bilateral perinephritis increased both systolic and diastolic blood pressure by about 30 mm Hg. Renal artery stenosis approximately doubled, but bilateral perinephritis did not change plasma renin activity. Both hypertensive groups, to about the same degree, had significantly more extensive atherosclerosis than the control group in the abdominal aorta and brachial, iliac-femoral, and carotid arteries. The effect of hypertension was greatest in the carotid arteries where the extent of atherosclerosis was nearly tripled. Hypertension did not influence lesions in the thoracic aorta. By multiple regression analysis, very low plus low density lipoprotein cholesterol, high density lipoprotein cholesterol, and systolic blood pressure were consistently strong predictive variables for the extent of atherosclerotic lesions. Most of the effects of renal hypertension on atherosclerotic lesions appeared to be accounted for by the increase in blood pressure. In the carotid arteries, however, there was a suggestion of an effect above that due to increased blood pressure. Additional analyses indicated that these treatment effects were associated with serum potassium concentration, plasma renin activity, or other closely related variables.

Animals↗

Dietary effects on serum lipoproteins of dyslipoproteinemic baboons with high HDL1.

Some progeny of baboons (Papio sp.) selectively bred for a high response of serum cholesterol to an atherogenic diet have high serum levels of unusual lipoproteins with flotation rates of F degrees 1.20 9-28, intermediate between those of low and high density lipoproteins (HDL). They are similar to the fraction of HDL commonly called HDL1. We conducted a cross-over experiment to determine the roles of dietary cholesterol and saturated fat in eliciting these lipoproteins in the progeny of two affected sires. Half of the progeny of each sire manifested the trait (high HDL1 phenotype) while consuming an atherogenic diet and half did not (low HDL1 phenotype). While consuming a chow diet, high HDL1 progeny had higher total serum cholesterol concentrations than did low HDL1 progeny. This difference was exaggerated when the animals consumed diets enriched in either cholesterol or saturated fat (lard), and was greatest when the diet contained both. High HDL1 animals also had considerably higher serum apo E concentrations, and slightly higher serum apo A-I concentrations. High HDL1 progeny had much higher levels of cholesterol (twofold) and of apo A-I (three- to eightfold) in HDL1 fractions than did low HDL1 progeny. There were significant interactions between HDL1 class and both dietary cholesterol and saturated fat in their effects on other lipoprotein fractions. High HDL1 animals had an exaggerated elevation of cholesterol and apo B in very low, intermediate, and low density lipoproteins in response to dietary cholesterol. They also had an exaggerated elevation of cholesterol in the lighter HDL1 fraction (d = 1.041-1.053), and lesser elevation of cholesterol and apo A-I in HDL2.

Animals↗

Effects of selective breeding on the cholesterolemic responses to dietary saturated fat and cholesterol in baboons.

Positive assortative mating of baboons (Papio sp.) based on elevation of serum cholesterol concentrations in response to a cholesterol- and saturated fat-enriched diet produced 64 progeny (30 high line; 34 low line). When the animals were 3 to 4 years of age, we tested their lipoprotein cholesterol responses to dietary cholesterol and fat in a factorial experiment with two levels of dietary cholesterol (1.7 and less than 0.01 mg/kcal) and two types of fat, coconut oil (P/S 0.1) and corn oil (P/S 3.5), each providing 40% of total calories from fat; we also tested their responses to chow. The high line animals had significantly higher very low density plus low density lipoprotein (VLDL + LDL) and high density lipoprotein (HDL) cholesterol levels on all diets. The effects of dietary cholesterol on VLDL + LDL cholesterol concentrations were greater in high line animals than in low line animals, but dietary cholesterol's effects on HDL cholesterol were similar in both lines. The effects of saturated fat, compared to unsaturated fat, on both VLDL + LDL and HDL cholesterol levels were similar in both lines. Selective breeding produced lines diverging in lipoprotein cholesterol concentrations by acting on several different genetically mediated processes that control serum lipoprotein levels. At least one of these processes involves responsiveness of serum VLDL + LDL cholesterol concentration to dietary cholesterol.

Age Factors↗

Deferred effects of preweaning diet on atherosclerosis in adolescent baboons.

We examined the effects of breast and formula feeding during infancy on the serum lipoproteins and on atherosclerosis in young adult baboons. Baboons were breast-fed (n = 13) or formula-fed (n = 32) until weaning at 16 weeks of age and thereafter they were fed a diet containing 1.7 mg cholesterol/kcal and 40% of calories as lard until 5 years of age. At 12 weeks of age, breast-fed baboons had higher serum high density lipoprotein cholesterol concentration (HDL-C, 68 vs. 51 mg/dl), lower serum triglyceride concentration (37 vs. 68 mg/dl), and lower very low density plus low density lipoprotein cholesterol (VLDL + LDL-C) to HDL-C ratio (0.65 vs. 0.98) than formula-fed infants. From weaning to 92 weeks of age, breast-fed baboons had a lower serum triglyceride concentration (23 vs. 38 mg/dl) than formula-fed baboons. After weaning, the VLDL + LDL-C/HDL-C ratio increased from 0.65 to 1.0 in breast-fed baboons, but decreased from 0.98 to 0.72 in formula-fed baboons. From 92 to 246 weeks of age, the VLDL + LDL-C/HDL-C ratio was consistently higher in breast-fed baboons compared to formula-fed baboons. At 5 years of age, baboons breast-fed as infants had a greater percentage of intimal surface area involved with atherosclerosis in the abdominal aorta, the iliac-femoral artery, the aortic arch, the brachial artery, and the carotid artery, than did those formula-fed as infants. The greater prevalence of lesions in breast-fed baboons was explained mainly by the higher VLDL + LDL-C/HDL-C ratio.

Animals↗