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S M Innis

Publications and source records attributed to S M Innis.

At least 73 records · Page 4Linked to original sources

Effects of developmental changes and early nutrition on cholesterol metabolism in infancy: a review.

Plasma cholesterol levels usually range between 50 and 100 mg/dl at birth, with the cholesterol approximately equally distributed between low-density lipoprotein (LDL) and high-density lipoprotein (HDL). Plasma cholesterol increases rapidly over the first days after birth, predominantly due to an increase in cholesterol with LDL, irrespective of whether the infant is breast fed or fed with infant formulas. With continued feeding, plasma cholesterol becomes progressively, and significantly, higher in infants who are breast fed compared to those fed low-cholesterol, polyunsaturated fatty acid-rich infant formula. Studies in the developing young of other species have suggested that up-regulation of cholesterol synthesis, or turnover and excretion, at stages when these pathways are acquiring functional maturity may have lasting effects on cholesterol metabolism. The information available, however, indicates the diet-related differences in plasma cholesterol of the more mature human newborn are temporal in nature and probably not of significance to adult cardiovascular disease. Infants born early in the third trimester of gestation, however, are at risk for marked elevations in plasma cholesterol, with stimulation of endogenous cholesterol biosynthesis, as a result of the intravenous nutrition required to sustain life. Whether this has long-term consequences for this group of infants is unknown. There is presently no reason to advocate diet modification to alter the plasma cholesterol of normal infants under the age of 2 years.

Animals↗

Arachidonic acid concentrations in plasma and liver phospholipid and cholesterol esters of piglets raised on formulas with different linoleic and linolenic acid contents.

The influence of sow milk or infant formulas containing 18:2n-6 and 18:3n-3 (% fatty acids) at 30/1, 16/1, 35/4, or 16/4 on plasma and liver phospholipid (PL) and cholesterol ester (CE) arachidonic acid (20:4n-6) was studied in piglets fed from birth for 15 d. Piglets fed the 35/4, 16/1, and 16/4 formulas had a significantly lower percentage of plasma 20:4n-6 in PL than did piglets fed sow milk or the 30/1 formula. The lowest plasma PL 20:4n-6 was in the 16/4 group, the only group in which liver PL 20:4n-6 was significantly reduced. This suggests competitive inhibition of synthesis or acylation of 20:4n-6 when formula with a high content of 18:3n-3 is fed in conjunction with a low content of 18:2n-6. The percentage of plasma CE 20:4n-6 was not altered by formula feeding. In contrast, the liver CE 20:4n-6 was significantly lower in all formula-fed animals than it was in sow-milk-fed animals. These studies confirm that 20:4n-6 metabolism is altered in artificially fed neonates. Liver and plasma cholesterol concentrations were also significantly lower in all formula-fed than in milk-fed piglets. The potential relationship of the decrease in cholesterol to n-6 fatty acids in CE is unknown.

Animals↗

Oleic acid (18:1) in plasma, liver and brain myelin lipid of piglets fed from birth with formulas differing in 18:1 content.

Recent studies have shown reduced 18:1 fatty acids in brain total lipid of piglets fed formula with 17% 18:1 fatty acids rather than sow milk providing 37% 18:1. Because 18:1 is a major fatty acid in brain myelin lipid and is rapidly deposited during myelination, it is important to know if this reflects deposition of myelin lipid containing reduced 18:1 and/or delayed myelination, or is related to changes in other brain membranes. Therefore, these studies determined the myelin total lipid, phosphatidylethanolamine and plasma and liver phospholipid fatty acids in piglets fed from birth to 15 d with formula containing (g/100 g fatty acids): 18:1, 17 and 18:3(n-3), 0.8; 18:1, 38 and 18:3(n-3), 0.6 fatty acids; or 18:1, 40 and 18:3(n-3), 4; or sow milk. Different levels of formula 18:3(n-3) fatty acids were studied because of the known effect of essential fatty acid deficiency on myelination. The brain 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase) activity and cerebroside concentration were also determined and used as indicators of myelination. Piglets fed the low 18:1 formula had lower 18:1 fatty acids in their plasma and liver phospholipid than sow milk-fed piglets. Formula providing a similar level of 18:1 to sow milk resulted in higher 18:1 fatty acids in the piglet plasma and liver phospholipid than in the sow milk-fed piglets. The brain myelin monoenoic fatty acids, CNPase activity and cerebroside concentration were similar in sow milk- and formula-fed piglets, irrespective of the formula 18:1 or 18:3(n-3) content.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Elevation of plasma lathosterol, as an indicator of increased cholesterol synthesis, in preterm (23-32 weeks gestation) infants given Intralipid.

Hypercholesterolemia is common in preterm infants administered 10% Intralipid perhaps because of excess phospholipid in plasma causing efflux of cholesterol from tissues. The purpose of this study was to determine if cholesterol synthesis (as measured by plasma lathosterol) is increased in preterm infants (23-32 wk gestation) during infusion of up to 4 g 10% Intralipid/kg body wt/d. Two groups of infants were studied. Intralipid intake was compared to: 1) plasma cholesterol in blood sampled over the first 100 d of life (preliminary study, n = 22) and 2) plasma cholesterol, lathosterol, and apo AI and B in blood taken at birth (cord), d 3-4 of life, and at least three additional times over the next 25 d (lathosterol study, n = 22). Lathosterol was quantitated by gas liquid chromatography and apo AI and B by immunoprecipitation. In the preliminary study, plasma cholesterol levels rose (to 4.06-10.70 mM) with Intralipid administration. Infants who received less than 2 g Intralipid/kg body wt/d were not hypercholesterolemic. In the lathosterol study, plasma cholesterol increased (1.86-2.24 mM, p = 0.06) and apo AI and B did not change, but lathosterol and the cholesterol:lathosterol ratio decreased (5.24-2.88 microM, p = 0.01, and 284-124 10(2) x mmol lathosterol:mol cholesterol, p = 0.007, respectively) from birth to d 3-4 (n = 11 paired samples). Infants followed longitudinally had increased cholesterol and lathosterol (4- to 7-fold) with increasing Intralipid administration, which decreased after discontinuation of infusion. Apo AI and B decreased upon Intralipid infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Plasma cholesterol and lathosterol levels in term infants in the early neonatal period.

Plasma cholesterol concentrations increase after birth. Whether this is due to increased cholesterol synthesis has not been reported. Additionally, it is not known if formulas, which lack cholesterol, result in higher rates of cholesterol synthesis than feeding breast milk. To address this, plasma lathosterol (quantitated by gas chromatography), a potential indicator of cholesterol synthesis, was measured in term infants at birth (cord) and 4 d of age fed either formula or breast milk (n = 6 each), normal adults (n = 6) at the expected nadir and peak of the diurnal rhythm (1700 h and 0830 h), and cholestyramine-treated hypercholesterolemic adults (n = 6). Plasma cholesterol and apo B increased, and apo AI (measured by immunoprecipitation) did not change over the first 4 d of life. The increase in plasma cholesterol was greater in the formula-fed infants compared with breast-fed infants. The plasma lathosterol concentrations (mumol/L) and the lathosterol:cholesterol ratios (10(2) x mmol lathosterol/mol cholesterol) decreased from birth to 4 d of age by 12 and 36%, respectively, in the breast-fed infants and by 20 and 46%, respectively, in formula-fed infants. The infant plasma lathosterol concentrations, however, were not different from normal adult levels [1700 h: 5.50 +/- 1.52 (SD); 0830 h: 6.18 +/- 1.80], but were lower than those of cholestyramine-treated adults (20.48 +/- 13.41). Sterol ratios of infants were higher than those of normal adults (1700 h: 112.5 +/- 26.0; 0830 h: 129.4 +/- 42.2), but not different from those of cholestyramine-treated adults (322.9 +/- 168.4).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Docosahexaenoic acid status of term infants fed breast milk or infant formula containing soy oil or corn oil.

The objective of this study was to compare circulating lipid docosahexaenoic acid [22:6(n-3), DHA] levels in term infants fed a powdered (CORN oil) or liquid (SOY oil) infant formula or human milk (HM). Infants whose mothers chose not to breast feed were randomly assigned to the CORN or SOY formula group. The formula fat differed in linolenic acid [18:3(n-3)] content: it was 0.8% for the CORN and 4.8% for the SOY. Linoleic acid [18:2(n-6)] was 31.5 and 34.2% fatty acids in the CORN and SOY formula, respectively. The formulas or HM were fed from birth through 8 wk of age, and growth and the plasma and red blood cell (RBC) phospholipid fatty acid composition was determined at 3 d, 4 wk, and 8 wk of age. Growth did not differ among groups. The plasma phospholipid and RBC phosphatidylethanolamine DHA was similar in the CORN and SOY formula groups at all ages. Plasma and RBC phosphatidylethanolamine levels of DHA were significantly lower in infants fed the CORN or SOY formula than in infants fed HM during wk 4 and 8. Plasma and RBC 22:5(n-6) was not increased in the formula groups at any age. The formula content of linolenic acid had no effect on the RBC or plasma DHA levels of the infants. The biologic or functional significance of the lower plasma and RBC DHA in infants fed formula rather than HM is unknown. The need for a dietary source of DHA and specificity of plasma or RBC phospholipid DHA as a measure of desaturation and elongation of linolenic acid in developing organs remains uncertain.

Corn Oil↗

Perinatal development of hepatic cholesterol synthesis in the rat.

Rates of cholesterol synthesis and HMG CoA reductase activity in rat liver, have been reported to be high before and low after birth. The timing of the decline in perinatal rates of cholesterol synthesis, however, is uncertain. These studies, therefore, determined in vivo rates of cholesterol synthesis using [3H]water and hepatic reductase activity in vitro in perinatal rats. The lipid composition of the plasma, liver and its microsomal subfraction were also determined. Reductase activity increased during late gestation, remained high immediately after birth, then decreased with the commencement of suckling. Rates of cholesterol synthesis increased from gestation day 18 to 20, but in contrast to reductase activity, decreased on the day before birth. Plasma cholesterol and triacylglycerol levels increased to gestation day 19, then decreased to term. By the 6th h after birth, plasma and liver cholesterol and triacylglycerol levels had increased markedly. By 48 h after birth, the high hepatic cholesterol content was associated with an increase in the cholesteryl ester fraction. The microsomal cholesterol/phospholipid molar ratio decreased from gestation day 16 until 12 h after birth, then increased markedly from 36 to 48 h. There was an apparent inverse relationship between the change in microsomal cholesterol/phospholipid molar ratio and the fatty acid unsaturation index from gestation day 16 to 36 h after birth. The results suggest that in late gestation and before suckling, the low in vivo rate of hepatic cholesterol synthesis may not be due to low activity of HMG CoA reductase.

Animals↗

Retina fatty acid composition of piglets fed from birth with a linoleic acid-rich vegetable-oil formula for infants.

The effects of a vegetable-oil-based formula containing 30% 18:2n-6 (18:2 omega-6), 0.8% 18:3n-3, and no n-6 or n-3 long-chain polyunsaturated fatty acids (LCPs) on retina total lipid, ethanolamine phosphoglyceride (EPG), and phosphatidylcholine (PC) fatty acid composition were studied in neonatal piglets. Term-gestation piglets were fed sow milk (SMF) or the formula (FF) from birth for 5, 10, 15, or 25 d. After 25 d feeding, the 22:6n-3 was reduced by 24% in total lipid, 20% in EPG, and 28% in PC of retinas of FF relative to SMF piglets. A compensatory increase in 22:4n-6 and 22:5n-6 concentrations occurred in retina total lipid, EPG, and PC of FF animals. The data suggest that the exclusive feeding of formulas devoid of LCPs and high in 18:2n-6 and/or 18:2n-6 and 18:3n-3 compromises normal accretion of 22:6n-3 in neonatal piglet retina. The potential reversibility of these changes or their effects on vision are not known.

Animal Feed↗

Effect of early introduction of formula vs fat-free parenteral nutrition on essential fatty acid status of preterm infants.

Previous studies have used relative (%) values of plasma 18:2n-6 (18:2 omega-6) and the ratio of 20:3n-9 to 20:4n-6 (triene/tetrene) to indicate the essential fatty acid (EFA: 18:2n-6 and 18:3n-3) status of preterm infants. The extent to which these indices reflect milligrams per liter quantities of n-6 and n-3 long-chain polyunsaturated derivatives of EFA (LCPs), required for cell membrane accretion, is unknown. Thus, 18:2n-6, the triene-tetrene ratio, and n-6 and n-3 LCPs were measured in plasma phospholipid of preterm infants' cord blood (n = 22) and of preterm infants fed formula (n = 12) or of preterm infants who received fat-free parenteral nutrition (n = 15) on postnatal day 3. Whether expressed as percent or milligrams per liter, 18:2n-6 was markedly higher and the triene-tetrene ratio lower in infants fed formula than in infants who had received no lipid. However, concentrations of n-6 and n-3 LCPs were similar in the two groups of infants and significantly higher than cord values. In the absence of an exogenous lipid source, it is suggested that tissue stores of LCPs are released in response to birth.

Birth Weight↗

Hepatic cholesterol and fatty acid synthesis in pregnant and fetal rats: effect of maternal dietary fat and cholestyramine.

Previous studies from this laboratory have demonstrated that 20% rather than 5% (wt/wt) safflower oil or addition of 5% (wt/wt) cholestyramine to the diet of pregnant rats leads to an increase in the activity of 3-hydroxy-3-methylglutaryl CoA reductase, the rate-limiting enzyme of cholesterol synthesis, in the fetal liver. Total cholesterol, however, was not altered in fetal plasma or liver. The effect of these diets on cholesterol and fatty acid synthesis in vivo was therefore studied in fetal and maternal liver. In fetuses of rats fed a reference nonpurified diet, rates of hepatic cholesterol and fatty acid synthesis decreased from gestation d 20 to 21. In contrast, total and active 3-hydroxy-3-methyl-glutaryl CoA reductase activity increased. Adding cholestyramine to the diet or modifying the quantity of safflower oil fed had no effect on fetal hepatic lipogenesis. Maternal hepatic cholesterol synthesis was greater in rats fed cholestyramine, whereas fatty acid synthesis was lower in the dams fed the diet containing 20% compared with 5% safflower oil. The results suggest near-term fetal liver 3-hydroxy-3-methylglutaryl CoA reductase activities do not reflect fetal cholesterol synthesis in vivo.

Administration, Oral↗

Response of (n-3) and (n-6) fatty acids in piglet brain, liver and plasma to increasing, but low, fish oil supplementation of formula.

Addition of fish oils to infant formula provides (n-3) long-chain polyenoic fatty acids (LCP), specifically 22:6(n-3), to infants fed formula rather than human milk. Most fish oils, however, contain high levels of 20:5(n-3) and low (n-6) LCP. These studies determined the brain total, synaptic plasma membrane phosphatidylethanolamine and phosphatidylcholine, and plasma and liver phospholipid fatty acids of piglets fed from birth to 15 d with formula containing (percent fatty acids) 34% 18:2(n-6), 0.8% 18:3(n-3) and 0, 2 or 6 g/L menhaden oil, or sow milk. The brain 22:6(n-3) was higher and 22:4(n-6) lower in piglets fed 6 g/L menhaden oil compared with sow milk. Brain levels of 20:5(n-3) did not increase, or levels of 20:4(n-6) decrease, with increasing dietary (n-3) LCP. A diet concentration-dependent increase in 20:5(n-3) and decrease in 20:4(n-6) (P less than 0.0001) in liver phospholipid showed no evidence of maximum saturation or depletion, respectively, over the range of (n-3) LCP intake studied. The fish oil supplementation was effective in supplying 22:6(n-3) to the developing brain. The accompanying increase in 20:5(n-3) and decrease in 20:4(n-6), important eicosanoid precursors, in plasma and liver phospholipid show the need for caution in the use of fish oils low in (n-6) LCP as a source of (n-3) LCP for infant formula.

Animals↗

Intralipid increases lung polyunsaturated fatty acids and protects newborn rats from oxygen toxicity.

Intralipid, derived from soybean oil and containing a high percentage of n-6 family polyunsaturated fatty acids (PUFA) and also linolenic acid, an n-3 family PUFA, is commonly the first fat source provided to very low birth weight premature infants. Following up on our previous reports that newborn rats born to dams fed high-PUFA diets demonstrate superior tolerance to hyperoxia, we examined whether the high-PUFA fat source Intralipid might also protect against oxygen toxicity. Adult female rats were fed either regular Rat Chow or fat-free diet containing 20%-Intralipid as the fat source for 3 wk before and then throughout pregnancy and lactation. One- and 5-d-old offspring of Intralipid diet-fed dams demonstrated significant increases in lung lipid n-6 family PUFA plus elevated linolenic acid compared with regular diet-fed offspring. These characteristic fatty acid patterns, apparent in total lung lipids, were even more pronounced in the triglyceride fraction compared with the phospholipid fraction. Associated with these fatty acid changes were significantly improved hyperoxic survival rates (89 out of 95 = 94% survival after 7 d of greater than 95% O2 exposure) in Intralipid offspring (versus 89 out of 106 = 84%, p less than 0.05 in regular diet offspring) and evidence of superior clinical/pathologic status. No differences in pulmonary antioxidant enzyme or surfactant system development, response of antioxidant enzymes to hyperoxic exposure, or lung prostaglandin E2, 6-keto PGF1-alpha or leukotrienes C4-F4 were present. These findings continue to support the hypothesis that increasing lung PUFA content may provide increased O2 free radical scavenging capacity, thus protecting against hyperoxic lung damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of a vegetable oil formula rich in linoleic acid on tissue fatty acid accretion in the brain, liver, plasma, and erythrocytes of infant piglets.

The effect of feeding sow-milk formula (SMF) or a vegetable-oil infant formula (FF) with minimal n-6 and n-3 long-chain polyenoic fatty acids (LCPs) but high linoleic acid (18:2n-6) and a high ratio of 18:2n-6 to linolenic acid (18:3n-3) on the fatty acids of brain lipid and liver, plasma, and red cell phospholipids was studied in piglets fed from birth for 5, 10, 15, or 25 d. Compared with SMF, FF reduced the concentrations of 18:1 and n-3 LCPs, especially 22:6n-3, in all tissues and increased 22:4n-6 in brain, liver, plasma, and red cell phosphatidylethanolamine. FF also increased 22:5n-6 in brain lipid, liver, and plasma but not in red cell phospholipids. Thus, changes in tissues capable of in situ desaturation were not completely reflected in the red cell phospholipids. The increased liver and brain n-6 LCP accretion in the FF piglets may suggest competent desaturation and possible inhibition of n-3 desaturation and/or acylation by dietary n-6 fatty acids.

Animals↗

Brain synaptosomal, liver, plasma, and red blood cell lipids in piglets fed exclusively on a vegetable-oil-containing formula with and without fish-oil supplements.

Clinical studies showed that a decrease in red blood cell 22:6n-3 caused by feeding infants formula (F) can be prevented by supplementation with fish oil (F + O). It is not known whether fish-oil supplementation is able to support normal accretion of fatty acids with greater than or equal to 20 carbons (LCPs) in the brain. Therefore piglets were fed exclusively F + O, F, or sow milk (SM) for 15 d and their liver and brain synaptosomal fatty acids were determined. Feeding F + O corrected the low n-3 LCP in the liver phospholipid (PL) and synaptosomal phosphatidylethanolamine (PE) of piglets fed F compared with SM. An apparent compensatory increase in n-6 LCPs in liver PL and synaptosomal PE of piglets fed F compared with SM was suppressed by feeding F + O. F + O also reduced the ratio of plasma PL 20:4n-6 to 20:5n-3, important for eicosanoid metabolism. Supplementation of F with n-3 LCPs as fish oil, without n-6 LCPs, at levels giving normal brain n-3 LCP, may alter n-6 LCP accretion.

Animals↗

Comparison of breast-feeding and formula feeding on intestinal and hepatic cholesterol metabolism in neonatal pigs.

Infant formulas (IFs) contain reduced cholesterol concentrations compared with breast milk (SM); how neonatal cholesterol metabolism responds to this difference is largely unknown. The effect of exclusive feeding of SM vs low-cholesterol IF on intestinal and hepatic cholesterol concentrations and synthesis during early postnatal development were compared in piglets. Animals were killed at birth or on days 5, 10, 15, or 25 postpartum. Plasma cholesterol concentrations were higher in SM-fed than in IF-fed piglets on days 15 and 25. In intestine both HMG-CoA reductase activity and 3H2O incorporation rates into cholesterol were similar for both groups or reduced in the IF-fed group at days 15 and 25. In liver, HMG-CoA reductase activity was higher in IF-fed than in SM-fed piglets on days 5, 10, and 15. Results indicate that during the early postpartum period, response to lower cholesterol intakes with IF occurs by increasing hepatic sterol synthesis whereas intestinal synthesis is largely unaffected.

Animals↗

Plasma and red blood cell fatty acids of low-birth-weight infants fed their mother's expressed breast milk or preterm-infant formula.

The fatty acid composition of plasma phospholipids, red blood cell (RBC) phosphatidylcholine (PC), and phosphatidylethanolamine (PE) was determined for low-birth-weight (LBW) infants when full oral feeding commenced (day 0) and after a further 28 d (day 28). They were fed their mother's expressed breast milk (PTM, n = 9), formula (SCF, n = 16) with 2% 18:3n-3 fatty acids, 20% 18:2n-6 fatty acids, or a combination of SCF and PTM (n = 11). Concentrations of all 20- and 22-carbon n-6 and n-3 fatty acids were similar among the infant groups on days 0 and 28 (mean postnatal age 42 +/- 1.3 d). The results suggest that formula with greater than or equal to 2% 18:3n-3 and a ratio of 18:2n-6 to 18:3n-3 similar to that of human milk may permit incorporation of n-3 fatty acids in LBW infant tissues equivalent to that from human milk.

Erythrocytes↗

Effect of dietary fat content and composition during pregnancy on fetal hepatic HMG CoA reductase activities and lipids in rats.

The effects of diets containing 20% (wt/wt) safflower, olive or palm oil or 5% (wt/wt) safflower oil when fed throughout gestation on hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity and on plasma and liver lipids were studied in fetal rats at d 21 of gestation. Hepatic total and active HMG CoA reductase activity, plasma free cholesterol and liver triglyceride and phospholipid 18:2(n-6) levels were higher in fetuses of rats fed 20% than in those of rats fed 5% safflower oil. Fetuses of rats fed olive oil had higher active HMG CoA reductase levels than fetuses of rats fed 20% safflower or palm oil; their total reductase activity was similar to that of the safflower oil group and higher than that for the palm oil group. Fetal liver and plasma cholesterol and triglyceride, as well as liver phospholipid concentrations, were not altered by the type of oil fed. The diets containing safflower oil resulted in higher 18:2(n-6) and lower 18:1 levels in fetal liver phospholipid and triglycerides than did the diets containing palm or olive oil. These studies demonstrate that fetal liver HMG CoA reductase activity is influenced by the maternal diet fat content and composition although the effect of specific fatty acids is unknown.

Animals↗