Biomedical subjects

D S Lewis

Publications and source records attributed to D S Lewis.

At least 19 recordsLinked to original sources

PubMed2000

Developmental changes in cholesterol 7alpha- and 27-hydroxylases in the piglet.

Hepatic cholesterol 7alpha-hydroxylase (CYP7A) and sterol 27 hydroxylase activities were measured in fetal, newborn, suckling, and weaned piglets from 76 d into gestation to 49 d of age. Hepatic CYP7A activity was not detected in fetal microsomes, but it increased to 6.8 +/- 2.6 pmol/min x mg(-1) protein in suckling piglets at 21 d of age and to 18.2 +/- 2.5 in weaned piglets at 49 d of age. Hepatic CYP7A activity was not different between 49-d-old piglets weaned at 21 d and piglets suckled for 49 d (18.9 +/- 2.6 and 18.2 +/- 2.5 pmol/min x mg protein, respectively). Fasting for 14 h decreased CYP7A activity by 86% in both suckled and weaned piglets. Cholesterol 7alpha-hydroxylase activity remained decreased for at least 5 h after refeeding. Sterol 27-hydroxylase activity was also undetectable near birth, but was detectable by 21 d of age. Postnatally, sterol 27-hydroxylase activity was not influenced by age or suckling and weaning, as was CYP7A. Sterol 27-hydroxylase was decreased by 80% in piglets deprived of feed compared with piglets given free access. In contrast to CYP7A activity, 27-hydroxylase activity returned within 5 h after refeeding to levels observed in piglets given ad libitum access to feed. Similar to CYP7A enzyme activity, hepatic CYP7A mRNA was not detected in newborn piglets, but increased from 2.7 +/- 1.7 pg mRNA/microg RNA in suckling piglets at 21 d to 13.7 +/- 1.2 in 49-d-old piglets weaned at 21 d. As with enzyme activity, feed deprivation decreased CYP7A mRNA to barely detectable levels (< .5 pg/microg RNA), and which remained decreased for at least 5 h following refeeding (.6 +/- .3 and 2.67 +/- .4 pg mRNA/microg RNA for suckled and weaned piglets, respectively). In piglets allowed free access to feed, CYP7A mRNA concentrations were associated positively (P = .001) with enzyme activity. These results suggest that developmental regulation of CYP7A activity is the result of a pretranslational mechanism.

Animals↗

PubMed1996

Resveratrol promotes atherosclerosis in hypercholesterolemic rabbits.

The hypothesis was tested that resveratrol, a compound in red wine, would inhibit atherosclerotic development in rabbits fed 0.5% cholesterol for 60 days. Rabbits were supplemented with or without oral resveratrol. During the study, body weights and food consumption were similar for the two groups. The lack of differences between liver weights and a series of serum parameters indicative of liver disease suggest that liver function was similar in the two groups. The diet produced hypercholesterolemia in both groups, but no differences in lipoprotein-cholesterol concentrations. The electrophoretic mobility of plasma low-density lipoprotein (LDL) and plasma LDL after induced oxidation also was not different between the groups. Staining of atherosclerotic lesions in the control and resveratrol-treated groups revealed that the resveratrol-treated rabbits had significantly more aortic surface area covered by atherosclerotic lesions (P < 0.02). Therefore, resveratrol promoted atherosclerotic development, rather than protect against it, by a mechanism that is independent of observed differences in gross animal health, liver function, plasma cholesterol concentrations, or LDL oxidative status.

Animals↗

PubMed1996

Early determinants of adult metabolic regulation: effects of infant nutrition on adult lipid and lipoprotein metabolism.

In a series of experiments over the past 20 years, we have demonstrated long-term deferred effects of infant nutrition, particularly breast- as compared with formula-feeding and overfeeding as compared with normal or underfeeding, on serum HDL-cholesterol concentrations, adiposity, and atherosclerosis in the baboon, a large nonhuman primate. Low HDL-cholesterol levels and obesity are associated with accelerated progression of atherosclerosis and with increased risk of coronary heart disease in humans. We have observed other deferred effects of infant nutrition on bile acid metabolism, enzyme activities, and water and electrolyte balance, some of which may be physiologically related to HDL-cholesterol levels or to adiposity. The occurrence of these deferred effects suggests that infant nutrition may program other metabolic systems for life, and that these effects may contribute to other chronic diseases of adults. Although our understanding of the mechanisms by which infant diet regimens affect adult metabolism is meager, it is important to identify these mechanisms because they are likely to provide valuable clues to the causes and ultimately may contribute to the long-range prevention of those diseases.

Adult↗

PubMed1996

Preweaning diet programs postweaning plasma thyroxine concentrations in baboons.

We tested the hypothesis that breast- and formula-feeding of infant baboons affect postweaning plasma thyroid hormone concentrations and that differences in thyroid hormone concentrations are associated with long-term effects of infant diet on lipoprotein concentrations and cholesterol metabolism. Newborn baboons were breast-fed (n = 12) or fed formulas with a high polyunsaturated/saturated (P/S) fat ratio (n = 11) or with a low P/S ratio (n = 12) similar to baboon breast milk. Baboons were weaned at 14 weeks of age to a high cholesterol, saturated fat diet. Plasma thyroid hormone concentrations were measured in this group of baboons until about 223 weeks of age. Thyroid hormones were also measured at 400 weeks in a second group of adult baboons (n = 80) that as infants were either breast-fed or fed formulas with varying levels of cholesterol. Baboons breast-fed as infants averaged 11% higher (P < 0.03) thyroxine (T4) concentrations from 34 to 400 weeks of age compared with those fed formulas. From 70 to 400 weeks of age breast-fed baboons had 10% lower T3/T4 ratios (P < 0.03). Breast- versus formula-feeding did not affect postweaning T3 and fT3 concentrations. Postweaning thyroid hormone concentrations were not significantly affected by the P/S ratio or the cholesterol level of the infant formulas. The rank correlation of the means of the sire progeny groups for T4 and HDL-C concentrations was statistically significant (rn = -0.83; P < 0.05). Partial correlations of T4 concentrations with body weight, feed intake, or measures of cholesterol metabolism were not significant. T4 concentrations were significantly correlated with T3 concentrations (r = 0.42; P < 0.02), and T3 concentrations were correlated with bile acid synthesis rate (r = 0.47; P < 0.01), acyl-CoA cholesterol acyltransferase (r = 0.66; P < 0.001), and plasma HDL1-C levels (r = -0.49; P < 0.007). These effects suggest that altered thyroid hormone homeostasis may partially mediate the long-term differences in cholesterol metabolism caused by breast-versus formula-feeding.

Animal Nutritional Physiological Phenomena↗

PubMed1995

Relationships of plasma and hepatic variables with rates of plasma low-density lipoprotein apolipoprotein B metabolism in baboons fed low- and high-fat diets.

These studies were conducted to determine relationships of plasma low-density lipoprotein (LDL) cholesterol concentrations and hepatic mRNA levels for apolipoprotein (apo) B, LDL receptor, and hepatic hydroxymethyl glutaryl coenzyme A (HMG CoA) synthase with plasma LDL apo B production and catabolic rates in baboons maintained on a low-cholesterol, low-fat chow diet and on a high-cholesterol, high-fat (HCHF) diet. Twelve baboons with LDL cholesterol levels ranging from low to high on the HCHF diet but with similar high-density lipoprotein (HDL) cholesterol levels were selected from a colony of selectively bred pedigreed baboons. LDL apo B turnover and hepatic mRNA concentrations for apo B, LDL receptor, and HMG CoA synthase were measured on a chow diet and again on a HCHF diet fed for 14 weeks. LDL apo B fractional catabolic rates decreased and production rates increased on the HCHF diet. Hepatic mRNA concentrations for apo B were not affected by the HCHF diet. Hepatic LDL receptor and HMG CoA synthase mRNA concentrations decreased on the HCHF diet as compared with the chow diet. LDL apo B fractional catabolic rate was negatively correlated with plasma cholesterol, LDL cholesterol, LDL apo B, and LDL apo B production and positively correlated with hepatic LDL receptor and HMG CoA synthase mRNA concentrations and with plasma LDL triglyceride to cholesterol ratio on the chow diet but not on the HCHF diet. LDL apo B production was positively correlated with plasma cholesterol, LDL cholesterol, and LDL apo B on the HCHF diet and negatively correlated with LDL triglyceride to cholesterol ratio on both chow and HCHF diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Triiodothyronine accelerates maturation of bile acid metabolism in infant baboons.

We tested the hypothesis that triiodothyronine (T3) treatment accelerates the early postnatal maturation of bile acid metabolism in the baboon. Infant baboons were implanted with 21-day-release pellets containing T3 (n = 12), a placebo pellet (n = 6), or no pellet (n = 13). T3 treatment increased plasma T3 concentrations from 3.0 to 5.0 nmol/l between birth and 15 wk of age. At 15 wk of age, bile acid pool sizes, fractional turnover rates (FTR), and synthetic rates were determined by an isotope-dilution method with 3H- and 14C-labeled cholic (CA) and chenodeoxycholic acid (CDCA). T3 treatment increased CA pool size by 47% and CA synthetic rate by 37% but did not significantly affect CDCA pool size or synthetic rate. Consequently CA-to-CDCA pool size ratio (0.77 vs. 0.42) and biliary CA-to-CDCA concentration ratio (0.88 vs. 0.46) were higher in the T3-treated infants than in combined placebo-treated and nontreated control infants. T3 treatment did not affect the bile acid glycine-to-taurine conjugate ratio, CA FTR, or CDCA pool size, FTR, and synthetic rate. T3 treatment lowered plasma high-density lipoprotein fraction 2 and 3 cholesterol concentrations by 22 and 40%, respectively. T3 treatment also increased hepatic low-density lipoprotein receptor mRNA levels but did not affect plasma low-density lipoprotein cholesterol concentrations. We conclude that modest elevation of plasma T3 during the preweaning period increases the CA-to-CDCA ratio at the end of the preweaning period to near adult values.

17-Hydroxycorticosteroids↗

PubMed1995

Differences in cholesterol metabolism in juvenile baboons are programmed by breast- versus formula-feeding.

We estimated the effects of breast- and formula-feeding on cholesterol and bile acid metabolism for 1.5 years after weaning in 35 newborn baboons that were breast-fed (n = 12) or fed one of two formulas with high (n = 11) or low (n = 12) polyunsaturated/saturated (P/S) fatty acid composition. Infants were weaned at 15 weeks to a high cholesterol, saturated fat diet. Because formula P/S ratio did not affect any variable for 1.5 years after weaning, the data were averaged for the two formula groups. After weaning, serum cholesterol and lipoprotein cholesterol concentrations among the infant diet groups were not different until after 52 weeks of age. From 70 to 97 weeks of age, serum cholesterol and high density lipoprotein-2 (HDL2)-cholesterol (HDL2-C) concentrations were lower (P < 0.04) among baboons that were breast-fed as infants compared with those fed formulas. We observed no significant postweaning differences in low density lipoprotein (LDL)-C, HDL3-C, or serum apolipoprotein A-I, B, or E concentrations. At 97 weeks of age baboons that were breast-fed until 15 weeks compared with those formula-fed had a 25% lower total bile acid synthetic rate (36.6 vs. 48.6 mumol/day per kg body weight, P < 0.02) due principally to a 29% lower cholic acid synthetic rate (23.2 vs 32.5 mumol/day per kg body weight, P < 0.004). Baboons breast-fed as infants had a 44% higher hepatic LDL-receptor mRNA concentration than those formula-fed (1.45 vs. 1.01 pg mRNA/micrograms total RNA, P < 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Effect of dietary lipids on plasma activity and hepatic mRNA levels of cholesteryl ester transfer protein in high- and low-responding baboons (Papio species).

We compared the effects of dietary cholesterol, type of fat (coconut oil v corn oil), and phenotype (low low-density lipoprotein [LDL] response v high LDL response) on the plasma activity and hepatic mRNA levels of cholesteryl ester transfer protein (CETP). In a crossover design, eight high- and eight low-LDL-responding baboons were fed a series of diets with increasing amounts of cholesterol (0.05, 0.15, 0.45, and 1.35 mg/kcal) with either coconut oil or corn oil. All diets were fed for 7 weeks each. plasma and lipoprotein cholesterol concentrations, plasma lecithin:cholesterol acyltransferase (LCAT) and CETP activity, and hepatic mRNA levels for CETP and apolipoprotein (apo) A-I were measured after 6 weeks on each diet. Data were analyzed in two steps, ie, the effect of the initial change from chow to 0.05 mg cholesterol with each fat and the effect of the stepwise increase in cholesterol from 0.05 to 1.35 mg/kcal with each fat. High-responding baboons, as expected, showed a more pronounced increment in plasma LDL cholesterol at all dietary cholesterol levels, particularly with coconut oil as the dietary fat. Plasma high-density lipoprotein 2 (HDL2) and HDL3 cholesterol increased as dietary cholesterol increased on both the coconut and corn oil diets, with a greater increase in high-responding baboons than in low-responding baboons. The stepwise increase in dietary cholesterol increased plasma LCAT activity in both high- and low-responding baboons fed the coconut oil diet, but not in those fed the corn oil diet. Dietary cholesterol, regardless of type of fat, increased plasma CETP activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Amino acid composition of human milk is not unique.

To determine whether the amino acid pattern of human milk is unique, we compared the amino acid pattern of human milk with the amino acid patterns of the milks of great apes (chimpanzee and gorilla), lower primates (baboon and rhesus monkey) and nonprimates (cow, goat, sheep, llama, pig, horse, elephant, cat and rat). Amino acid pattern was defined as the relative proportion of each amino acid (protein-bound plus free) (in mg) to the total amino acids (in g). Total amino acid concentration was lower in primate milk than in nonprimate milk. There were commonalities in the overall amino acid pattern of the milks of all species sampled; the most abundant amino acids were glutamate (plus glutamine, 20%), proline (10%) and leucine (10%). Essential amino acids were 40%, branched-chain amino acids 20%, and sulfur amino acids 4% of the total amino acids. The amino acid pattern of human milk was more similar to those of great apes than to those of lower primates. For example, cystine was higher and methionine was lower in primate milks than in nonprimate milks, and in great ape and human milks than in lower primate milks. Because the milk amino acid patterns of the human and elephant, both slow-growing species, were dissimilar, the amino acid pattern of human milk seems unrelated to growth rate.

Amino Acids↗

PubMed1994

Metabolic mechanisms for responses to dietary cholesterol and fat in high and low LDL responding baboons (Papio sp.).

These studies were conducted to determine how plasma low density lipoprotein (LDL) cholesterol levels respond to dietary cholesterol, fed in increasing amounts with either corn oil or coconut oil diets, in high as compared to low LDL responding baboons; and to determine how apolipoprotein (apo) B transcription levels are modulated in response to dietary lipids. Eight high and eight low LDL responding pedigreed adult baboons, balanced for sire, age, sex, and weight, were challenged for successive 7-week periods with increasing levels of dietary cholesterol combined with either coconut oil or corn oil. At the end of each dietary period, plasma and lipoprotein lipids, apoB, apoA-I, and hepatic mRNA levels for apolipoproteins were measured. As dietary cholesterol increased, plasma cholesterol concentrations (mostly LDL cholesterol) increased in both phenotypes and with both types of fat, but phenotypic differences were greater with coconut oil. There was not a consistent dose-response relationship of plasma or LDL cholesterol levels to increasing intakes of dietary cholesterol. Neither dietary cholesterol, type of dietary fat, nor LDL phenotype affected hepatic apoB or apoE mRNA levels. In a second experiment to resolve the inconsistent dose-response to dietary cholesterol, we fed the animals varying levels of dietary cholesterol combined with coconut oil, and separated the challenge periods with intervening 12-week chow periods. Plasma and LDL cholesterol and apoB concentrations rose consistently with increasing dietary cholesterol, and the slope of the increase diminished at the higher doses. The results suggest that genetic differences in the initial response of LDL cholesterol to dietary cholesterol and saturated fatty acids are not due to the differences in hepatic transcription of apoB, and that the preceding dietary intake of cholesterol and saturated fatty acids is a major determinant of the response of plasma lipids and the associated metabolic processes to a dietary challenge. The response of baboon plasma LDL cholesterol concentrations to dietary cholesterol, when fed with saturated fatty acids, is similar to that of humans.

Animals↗

PubMed1993

Influence of breast and formula feeding on hepatic concentrations of apolipoprotein and low-density lipoprotein receptor mRNAs.

We tested the hypothesis that breast and formula feeding differentially affect hepatic mRNA concentrations for LDL receptor (LDL-R) and apolipoproteins A-I, B and E in infant baboons during the preweaning period. The mRNA concentrations were measured in liver biopsies obtained prior to weaning at 14 weeks from 43 baboons that were either breast-fed (n = 17) or fed formulas with a high (n = 12) or low (n = 14) polyunsaturated/saturated (P:S) fat ratio. Breast-fed baboons had 99% higher LDL-R mRNA concentrations compared with infants fed formulas, but there were no differences among breast and formula-fed baboons in mRNA concentrations of apolipoproteins A-I, B or E. The fatty acid P:S ratio of the formulas did not affect hepatic LDL-R or apolipoprotein mRNA concentrations. These results suggest that breast-feeding increases LDL-R gene expression even though breast milk is higher in cholesterol and saturated fat compared with formulas.

Animals↗

PubMed1993

In vivo and in vitro development of visceral adipose tissue in a nonhuman primate (Papio species).

We determined the development of the omental fat depot in a cross-sectional study of 242 baboons from birth to mature adulthood. The triglyceride content of the omentum increased during preweaning (birth to 4 months) and adolescence (2 to 5 years) and was associated with an increase in both fat cell number and size. Between weaning and 2 years of age omentum triglyceride mass decreased as a result of decreasing fat cell size, but fat cell number remained constant. After adolescence and up to 13 years of age, omental triglyceride mass and fat cell volume were stable, but fat cell number increased slightly in female baboons. We determined the in vitro potential of omental stromal vascular (S-V) cells from baboons at different stages of development to differentiate in a serum-free medium. Both the proportion of omental S-V cells that accumulated cytoplasmic lipid droplets and the induction of glycerol phosphate dehydrogenase (GPDH) activity were increased to the greatest degree in the presence of 1-methyl-3-isobutylxanthine, 2.0 nmol/L triiodothyronine (T3), 0.85 mumol/L insulin, and 1.0 mumol/L cortisol. Omental S-V cells from preweaning and adolescent baboons had a greater differentiation rate, GPDH activity, and triglyceride accumulation compared with cells from postweaned infants and mature adults. In summary, most of the growth of the baboon omentum occurs during the preweaning and pubertal periods of life, and omental S-V cells isolated from animals during these periods retain a greater potential to differentiate in vitro.

1-Methyl-3-isobutylxanthine↗

PubMed1993

The role of cholesterol absorption and hepatic cholesterol content in high and low responses to dietary cholesterol and fat in pedigreed baboons (Papio species).

Selective breeding has produced baboon families with low and high plasma cholesterol responses to dietary cholesterol and fat. We used 12 high- and 12 low-responding (mainly in low-density lipoprotein [LDL] cholesterol) pedigreed baboons to determine whether cholesterol absorption and hepatic cholesterol concentration are associated with these responses. We measured cholesterol absorption first on the chow diet, which was low in cholesterol and fat, and after 3 and 13 weeks on the challenge diets, which contained 0.45 mg cholesterol/kcal and 40% of calories as either coconut oil or corn oil. Plasma, lipoprotein, and hepatic cholesterol concentrations were measured 1 week after cholesterol absorption measurements. High-responding baboons had higher percentage cholesterol absorption than low-responding baboons on both chow and challenge diets, regardless of the type of dietary fat. Both high and low responders had higher percentage cholesterol absorption with corn oil than with coconut oil. High responders also had higher hepatic cholesterol concentrations than low responders on chow and after consuming the challenge diets for 4 weeks. After consuming the challenge diets for 14 weeks, low responders fed coconut oil had hepatic cholesterol levels equal to those of high responders, while low responders fed corn oil continued to have low hepatic cholesterol levels. Thus, percentage cholesterol absorption is consistently higher in high-responding baboons regardless of diet, but hepatic cholesterol concentration varies with duration of challenge and type of fat. The results suggest that both cholesterol absorption and hepatic cholesterol concentration regulate cholesterolemic responses to diet, but by different mechanisms.

Animals↗

PubMed1993

Infant diet affects serum lipoprotein concentrations and cholesterol esterifying enzymes in baboons.

We characterized the preweaning differences in cholesterol metabolism between breast-fed and formula-fed baboons and determined if formulas with low and high polyunsaturated:saturated fatty acid (P:S) ratios simulated the effects of breast feeding. At birth, 45 infant baboons from three sires and 44 dams were assigned to breast-fed, low P:S formula or high P:S formula diet groups until weaning at 14 wk. From 4 to 14 wk breast-fed infants had higher serum cholesterol because of much higher HDL1- and HDL2-cholesterol concentrations but had lower HDL3-cholesterol than both formula-fed groups. LDL-cholesterol was higher in infants fed the low P:S fomula. Breast-fed infants had higher serum apolipoprotein E than the formula-fed groups, but diet did not affect apolipoprotein A-I or B concentrations. Breast-fed infants had higher hepatic acyl CoA cholesterol acyltransferase activity and lower plasma lecithin cholesterol acyltransferase activity. These enzyme activities were not different between infants fed low or high P:S formulas. Post-heparinized plasma lipoprotein lipase activity was greater in breast-fed infants than in those fed formula. These findings demonstrate that the P:S ratio of formulas has little effect on cholesterol metabolism during the preweaning period and suggest that factors other than fat composition account for the metabolic differences between breast feeding and commercial infant formula.

Animals↗

PubMed1993

Preweaning diet affects bile lipid composition and bile acid kinetics in infant baboons.

We tested, with 14-wk-old baboons before weaning, the hypothesis that bile acid metabolism is differentially affected by breast feeding or by feeding formulas with a high polyunsaturated:saturated fatty acid ratio or with a low ratio, similar to that of breast milk. Bile lipid content, bile acid pool size, fractional turnover rate, synthetic rate and conjugate composition were measured in a single bile sample 9 d after an injection on d 1 of a mixture of [14C]cholic and [14C]chenodeoxycholic acids and an injection of a mixture of [3H]cholic acid and [3H]chenodeoxycholic acid on d 8. The principal biliary bile acid was chenodeoxycholic acid. The only difference in chenodeoxycholic acid metabolism among the infant diet groups was a lower chenodeoxycholic acid synthetic rate in baboons fed the low polyunsaturated:saturated formula compared with those fed the high polyunsaturated:saturated formula or breast-fed. Cholic acid metabolism was significantly affected by infant diet: breast-fed infants had a smaller cholic acid pool size, lower cholic acid percentage of total bile acids, higher cholic acid glycine:taurine conjugate ratio and larger cholic acid fractional turnover rate than formula-fed animals. The polyunsaturated:saturated fatty acid ratio in the formulas did not significantly affect these variables. These results show that differences in bile acid metabolism between breast- and formula-fed infant baboons are limited principally to cholic acid. These differences likely are due to factors other than fatty acid saturation.

Analysis of Variance↗

PubMed1993

Breast feeding and formula feeding affect differently plasma thyroid hormone concentrations in infant baboons.

We tested the hypothesis that plasma thyroid hormone levels in infant baboons are differentially affected by breast-feeding and nursery rearing. Infant baboons were breast-fed (n = 17), or fed formulas with a high polyunsaturated to saturated fat ratio (P/S) (n = 13), or a low P/S formula (n = 14). Plasma total triiodothyronine (T3) and free T3 (fT3) concentrations increased from 4 to 14 weeks of age in infants fed either formula, but decreased in breast-fed infants. At 9 and 14 weeks of age, infants fed the formulas averaged 31% higher T3 and 53% higher fT3 concentrations compared with breast-fed infants. Although T3 concentrations of the high P/S formula group compared with the low P/S formula group were not different at any single age, from 4 to 14 weeks the T3 averaged 19% higher in the high P/S formula group. Plasma total thyroxine (T4) or free T4 (fT4) concentrations were not significantly different among the diet groups during the preweaning period. In summary, formula-fed infants maintained higher plasma T3 and fT3 levels compared with breast-fed infants in the late preweaning period.

Analysis of Variance↗

PubMed1993

Effect of premature birth and survival on hepatic thyroxine 5'-monodeiodinase activity in baboons.

Plasma thyroid hormones and hepatic 5'-monodeiodinase type I (5'-MDI) activity were measured in a primate model of premature birth and survival. When prematurely delivered at 140 days (term gestation is 184 days), infant baboons developed hyaline membrane disease, had no surge in T3 and T4, temporarily developed hypothyroxinemia, and had extremely low T3 concentrations during the first 40 h of life. After 4 days, both plasma T4 and T3 levels progressively increased, but were still considerably lower at 16 days compared to those in normal term infants. Hepatic 5'-MDI activity was measured in the presence of dithiothreitol in fetal, premature, and infant baboons. Fetal baboons at 140 and 161 days gestation had 80% less 5'-MDI activity than term infants, but at 178-180 days gestation, near term, fetal hepatic 5'-MDI activity increased to levels similar to those in young adults. Interruption of in utero development by premature birth resulted in no change in hepatic 5'-MDI activity after 24 h, but within 6 days after delivery, hepatic 5'-MDI had significantly increased to levels observed in fetal baboons near term. Kinetic analysis revealed that fetal and premature 5'-MDI had different maximum velocities and similar apparent Km values. There was no significant difference in hepatic total, protein, or nonprotein sulfhydryl groups between 1- and 10-day-old premature (140 days gestation) baboons. These results suggest that premature birth does not limit the postnatal maturation of hepatic 5'-MDI activity.

Animals↗

PubMed1992

Effect of energy intake on postprandial plasma hormones and triglyceride concentrations in infant female baboons (Papio species).

We previously reported that female baboons overfed during infancy were not fatter at weaning, but developed hypertrophic obesity after puberty. To clarify the mechanisms of this dietary effect on adipocyte hypertrophy, we determined the effects of infant overfeeding on preweaning plasma hormone and triglyceride levels and their relationship with fat cell volume at weaning (19 weeks of age). Newborn female baboons from 3 sires and 24 dams were fed either 280 kilojoules (normally fed; n = 12) or 395 kilojoules (overfed; n = 10) per 100 g Similac formula for 18 weeks. Both formulas contained 9.2%, 43.1%, and 48.5% of calories as protein, carbohydrate, and fat, respectively. During the first 9 weeks, overfed infants had significantly higher fasting and postprandial insulin, total T3, and free T3 concentrations; lower cortisol levels; and lower excretion of urinary 17-hydroxycorticosteroids (17-OHCS) than normally fed infants. These effects were no longer significant at 17-18 weeks. Infant diet did not influence fasting and postprandial plasma triglyceride levels, and fat cell volume was not influenced by energy intake. However, fat cell volume was positively associated with postprandial triglyceride concentrations and inversely associated with postmeal nadir cortisol levels. These results demonstrate that infant overfeeding initiates early alterations in insulin, T3, free T3, and cortisol, but these effects persist only as long as there is a significant increase in energy intake.

17-Hydroxycorticosteroids↗