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Biomedical subjects

S M Innis

Publications and source records attributed to S M Innis.

At least 55 records · Page 3Linked to original sources

Formula 18:2(n-6) and 18:3(n-3) content and ratio influence long-chain polyunsaturated fatty acids in the developing piglet liver and central nervous system.

Docosahexaenoic acid and arachidonic acid are deposited in large amounts in the developing central nervous system, and concentrations are particularly high in synaptic plasma membrane and retina ethanolamine phospholipids. Arachidonic acid and docosahexaenoic acid are present in human milk. The precursors linoleic [18:2(n-6)] and alpha-linolenic [18:3(n-3)] acid, but not arachidonic acid or docosahexaenoic acid, are present in formulas. Desaturation and elongation of 18:2(n-6) and 18:3(n-3) to arachidonic acid and docosahexaenoic acid, respectively, depend on the dietary content and ratio of 18:2(n-6) and 18:3(n-3), but appropriate levels and ratios of 18:2(n-6) and 18:2(n-3) for formula are not well defined. The effect of formula with 1 or 4% fatty acids 18:3(n-3) and 16, 30 or 35% fatty acids 18:2(n-6) on synaptic plasma membrane and retina ethanolamine phospholipid fatty acids was therefore studied in piglets, with reference to piglets fed milk. Piglets fed 4% fatty acids 18:3(n-3), but not those fed 1% fatty acids 18:3(n-3), had similar central nervous system docosahexaenoic acid levels but had significantly lower brain weights than piglets fed sow milk. Synaptic plasma membrane and retina arachidonic acid were lower in piglets fed the formulas with 4% rather than 1% fatty acids 18:3(n-3). The dietary 18:3(n-3) content, rather than the 18:2(n-6) to 18: 3(n-3) ratio, seemed more important for deposition of docosahexaenoic acid in brain. However, synaptic plasma membrane and retina docosahexaenoic acid levels were further reduced in piglets fed 1% fatty acids 18:3(n-3) (0.4% energy) with 30% rather than with 16% fatty acids 18:2(n-6). The need for further study of upper limits of dietary 18:3(n-3) during development is suggested.

Analysis of Variance↗

The 1993 Borden Award Lecture. Fatty acid requirements of the newborn.

Arachidonic acid (20:4 omega-6) and docosahexaenoic acid (22:6 omega-3) are deposited in large amounts in the nonmyelin membranes of the developing central nervous system (CNS). Inadequate supplies of omega-6 and omega-3 fatty acids during CNS development are of concern because of possible long-term changes in learning ability and reduced visual function. Although all of the omega-6 and omega-3 fatty acids in the CNS are ultimately derived from the diet, the pathways for transport or transfer from the plasma to the CNS are not known. Current evidence suggests that the newborn is able to synthesize 20:4 omega-6 and 22:6 omega-3 from linoleic acid (18:2 omega-6) and linolenic acid (18:3 omega-33), respectively; however, it is not yet clear if synthesis occurs in the liver prior to transfer to the CNS, or directly in the CNS. Further understanding of the roles of 20:4 omega-6 and 22:6 omega-3 in CNS metabolism, pathways of omega-6 and omega-3 fatty acid transport and CNS uptake, and the effects of premature birth on fatty acid metabolism is needed to facilitate future studies on the importance of 20:4 omega-6 and 22:6 omega-3 in infant nutrition.

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A comparative study of hepatic HMG CoA reductase activity and LDL receptor relative mass in suckling and adult guinea pigs.

The reason why plasma cholesterol levels increase soon after birth is unknown but may be related to change rates of cholesterol synthesis and/or expression of LDL receptors. Plasma cholesterol levels, along with hepatic HMG CoA reductase activity, the rate-limiting enzyme of cholesterol synthesis, and hepatic LDL receptor relative mass were measured in suckling (1, 4 and 8 days of age) and adult guinea pigs. Plasma cholesterol was measured by an enzymatic assay, HMG CoA reductase activity was determined using a radiolabelled substrate and LDL receptor-relative mass was measured by ligand blotting with gold-labelled rabbit beta VLDL. Among the young animals, HMG CoA reductase activity and plasma cholesterol levels increased between 1 and 4 days of age. The LDL receptor mass did not change in the first 8 days after birth, but was 2-fold higher in adult than suckling animals. Hepatic HMG CoA reductase activity was also higher in the adult animals. Increased hepatic HMG CoA reductase and low LDL receptor mass may contribute to the elevation in plasma LDL cholesterol levels in the 4-day-old guinea pig.

Aging↗

Dietary saturated, monounsaturated, n-6 and n-3 fatty acids, and cholesterol influence platelet fatty acids in the exclusively formula-fed piglet.

Platelet lipid composition is important to normal platelet morphology and function, and is influenced by dietary fatty acids and cholesterol. The fatty acid composition and cholesterol content of infant formulas differs from those of human milk, but the possible effects on platelet lipids in young infants is not known. This was studied in piglets fed from birth to 18 d of age with one of eight formulas differing in saturated fatty acid chain length, or content of 18:1, 20:5n-3 plus 22:6n-3, or cholesterol. A reference group of piglets fed sow milk was also studied. Sow milk has a fatty acid composition and cholesterol content similar to that of human milk. Piglets fed formulas high in 18:1 (34.9-40.8% wt fatty acids) and low in 16.0 (< or = 6.5% wt fatty acids) had lower platelet counts and greater platelet size than piglets fed sow milk (40.4% 18:1, 30.7% 16:0). Piglets fed formulas high in 16:0 (27-29.6%) and 18:1 (40-40.6%), or low in both 16:0 (5.9-6.1%) and 18:1 (10.8-11.2%), had similar platelet counts and size to piglets fed sow milk. Platelet phospholipid % 20:4n-6 was lower in all the groups of piglets fed formula than in the group fed sow milk. Addition of fish oil with 20:5n-3 plus 22:6n-3 to the formula further decreased platelet phospholipid 20:4n-6. Addition of cholesterol to the formula increased the platelet phospholipid % 20:4n-6 and platelet volume.

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Cholesterol and fatty acid metabolism in piglets fed sow milk or infant formula with or without addition of cholesterol.

Several studies have reported that plasma cholesterol and phospholipid (PL) levels of arachidonic acid (20:4n-6) are lower and PL levels of linoleic acid (18:2n-6) are higher in infants fed formula than in infants fed human milk. Plasma cholesterol level and possibly the dietary intake of cholesterol could be related to plasma PLn-6 fatty acid metabolism because plasma PL 18:2n-6 is used for esterification of plasma free cholesterol. Whether the low cholesterol content of infant formula as compared with human milk is related to the difference in plasma n-6 fatty acid levels between infants fed human milk and infants fed formula is not known. This study determined the effect of feeding formula with 0.05 mmol cholesterol/L, formula with 1.09 mmol cholesterol/L, or sow milk with 0.34 mmol cholesterol/L on plasma, liver, and bile lipid fatty acid levels and liver low-density lipoprotein (LDL) receptor mass in piglets. Liver microsomal 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity and plasma lathosterol were assayed as indices of liver and body cholesterol synthesis, respectively. Formula with or without cholesterol added, or sow milk, was fed from birth to 18 days of age. Providing cholesterol in the formula did not correct the significantly lower plasma cholesterol or plasma and liver PL 20:4n-6 levels associated with formula feeding. The liver total cholesterol and cholesteryl esters (CE), biliary bile acid, and PL concentrations were significantly higher and the liver HMG CoA reductase activity and plasma lathosterol:cholesterol ratio were significantly lower in piglets fed the formula with cholesterol than in piglets fed the formula without cholesterol added.(ABSTRACT TRUNCATED AT 250 WORDS)

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Oxidized low-density lipoprotein in experimental focal glomerulosclerosis.

Oxidized low-density lipoproteins (Ox-LDL) have been shown to be involved in the pathogenesis of atherosclerosis. Because of the similarities between atherosclerosis and focal glomerulosclerosis, a study was performed to demonstrate whether Ox-LDL could be detected in the glomeruli in experimental FGS. FGS was induced in 12 rats on a 4% cholesterol-1% choline diet by seven injections of puromycin aminonucleoside over a 10 week period. Eight rats on a normal diet served as controls. Fourteen weeks after the start of the experiment all rats were sacrificed. The test animals showed marked hypercholesterolemia and proteinuria. About 20% of glomeruli in test animals showed FGS and variable amounts of glomerular lipid were demonstrated. Immunohistochemical staining using five specific monoclonal antibodies against various forms of Ox-LDL showed positive staining of a variable number of glomeruli in the test rats. The staining pattern appeared to be intracellular. Staining with ED1 showed significantly increased numbers of intraglomerular monocytes in the test rats (test vs. control 2.4 +/- 1.1 vs. 0.4 +/- 0.1 monocytes per glomerulus, P < 0.0001). Control animals showed no segmental sclerosis, no glomerular lipid, and no staining for Ox-LDL. Lipid analysis of isolated glomeruli showed increased cholesterol, increased arachidonic acid and decreased eicosapentaenoic acid in test animals compared to controls. The findings suggest a role for Ox-LDL in the pathogenesis of experimental FGS and support the hypothesis that FGS is analogous to atherosclerosis.

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Saturated fatty acid chain length and positional distribution in infant formula: effects on growth and plasma lipids and ketones in piglets.

Human milk contains a large proportion of palmitic acid (16:0) with > 70% esterified to the center sn-2 position of the milk triglyceride. Infant formulas often use 8:0 + 10:0 [medium-chain triglyceride (MCT)] or 12:0 + 14:0 (coconut oil) as the saturated fat. The effect of formula saturated fatty acid composition; 8:0 + 10:0, 12:0 + 14:0, or 16:0 from palm oil or synthesized triglyceride containing predominantly sn-2 16:0 on plasma lipids and fatty acids was studied in piglets. Although the formulas contained similar 18:1 and 18:2n-6, plasma lipid percentages of 18:1 and 18:2n-6 were higher in piglets fed the formula with MCT or coconut oil rather than the formulas with 16:0, or sow milk. The sn-2 16:0 of the synthesized triglyceride had unique properties. Specifically, piglets fed synthesized triglyceride had significantly higher cholesteryl ester 16:0 identical to that in piglets fed sow milk and higher plasma total and high-density-lipoprotein cholesterol than piglets fed the other formulas.

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Docosahexaenoic acid is transferred through maternal diet to milk and to tissues of natural milk-fed piglets.

Docosahexaenoic acid (DHA) is incorporated in large amounts in structural lipids of the developing central nervous system. Milk DHA varies with maternal dietary DHA, but the effect of different intakes of DHA from milk on infant tissue fatty acids is unknown. The effect of milk high or low in DHA on the fatty acid composition of piglet brain, synaptic plasma membranes, retina, liver, plasma and RBC was studied. Pregnant sows were fed diets with 2.5 g/100 g vegetable oil until 4 d pre-partum and were then fed diets with 2.5 g/100 g soybean and canola oils or 4 g/100 g soybean oil plus 1 g/100 g fish oil to 15 d postpartum. Fish oil increased the milk DHA and eicosapentanoic acid from 0.1 to 1.5% and from 0.2 to 0.4% of fatty acids, respectively, but did not alter milk arachidonic acid. The level of DHA was significantly higher in plasma, liver and RBC phospholipids, brain and synaptic plasma membrane of 15-d-old piglets fed milk with high DHA compared with low DHA. Liver, plasma and RBC, but not brain or retina arachidonic acid, was significantly lower in piglets fed the high DHA milk compared with low DHA milk. Thus, differences in plasma, RBC and liver arachidonic acid and DHA of 15-d-old nursing piglets due to the maternal dietary fat were not accompanied by similar differences in central nervous system fatty acids. These studies show maternal DHA intake determines in part the infant plasma, RBC and liver phospholipid DHA.(ABSTRACT TRUNCATED AT 250 WORDS)

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The colostrum-deprived piglet as a model for study of infant lipid nutrition.

The large proportions of arachidonic acid (20:4 omega-6) and docosahexaenoic acid (22:6 omega-3) in brain and retina structural lipids are important for normal central nervous system function. Study of dietary requirements for omega-6 and omega-3 fatty acids for brain growth is difficult in the human infant because of variabilities in human milk fatty acids, lack of correspondence between blood lipids and central nervous system (CNS) lipids and ethical limits of tissue analyses. Comparison of nutrient requirements, lipid digestion, absorption and transport and milk and brain lipids and the timing of intestinal maturation and the brain growth spurt during fetal-infant development show the piglet to be an excellent choice for studies relevant to lipid nutrition of term gestation infants. Of practical relevance, piglets are easily hand-fed and, with a relatively large body size and rapid growth, provide ample tissue for analyses of the effects of diet fat on specific CNS cell membranes. Use of the piglet to define omega-6 and omega-3 fatty acid requirements and the effects of addition of marine oils to formulas and the lactating mother's diet on the developing CNS are described.

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Essential fatty acid requirements in human nutrition.

Arachidonic acid (20:4 omega-6) and docosahexaenoic acid (22:6 omega-3) are major acyl components of cell membrane phospholipids, and are particularly enriched in the nonmyelin membranes of the central nervous system. Dietary deficiency of linoleic acid (18:2 omega-6) and linolenic acid (18:3 omega-3) during development has been shown to result in reduced levels of 20:4 omega-6 and 22:6 omega-3 in the developing central nervous system, and this has been associated with altered learning behaviour and visual function. Synthesis of 20:4 omega-6 and 22:6 omega-3 depends on the dietary intake of 18:2 omega-6 and 18:3 omega-3, respectively, and the activity of the fatty acid desaturase-elongase enzymes. Oxidation of 18:2 omega-6 and 18:3 omega-3 for energy, or direct acylation of 18:2 omega-6 into triglycerides, cholesteryl esters, and phospholipids, could also influence the amount of 20:4 omega-6 and 22:6 omega-3 formed. The tissue levels of 20:4 omega-6 and 22:6 omega-3, or other (omega-6) and (omega-3) fatty acids, compatible with optimum growth and development or health are not known. The amount of preformed 22:6 omega-3 in the diet of adults, infants fed various milks or formulae, or animals is reflected in the circulating lipid levels of 22:6 omega-3. Human milk levels of (omega-6) and (omega-3) fatty acids vary, depending in part on the mother's diet. A valid, scientific approach to extrapolate dietary essential fatty acid requirements from the composition of human milk or the circulating lipids of infants fed different diets has not been agreed on.(ABSTRACT TRUNCATED AT 250 WORDS)

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Formula alpha-linolenic (18:3(n - 3)) and linoleic (18:2(n - 6)) acid influence neonatal piglet liver and brain saturated fatty acids, as well as docosahexaenoic acid (22:6(n - 3)).

Saturated fatty acids can be synthesized de novo and play a role in determining properties of structural membranes. The effect of dietary essential fatty acids, linoleic acid (18:2(n - 6)) and alpha-linolenic acid (18:3(n - 3)), on the saturated fatty acid content of membrane phospholipid has not previously been considered in newborn nutrition. The studies report the effect of low (1% fatty acids) or high (4%) formula 18:3(n - 3) with low (16%) or high (30-35%) formula 18:2(n - 6) on the saturated and unsaturated fatty acid composition of liver and brain structural lipid of piglets fed formula from birth for 15 days. A significant inverse relationship between the formula % 18:3(n - 3), but not 18:2(n - 6), and the liver phospholipid palmitic acid (16:0) was found. This may indicate a possible effect of dietary 18:3(n - 3) on de novo synthesis of 16:0 and requires further investigation. Monounsaturated fatty acids in both liver and brain were significantly lower in response to high 18:3(n - 3) and to high 18:2(n - 6) plus low 18:1(n - 9) in the formula. Liver phospholipid and brain total lipid % docosahexaenoic acid (22:6(n - 3)) were significantly higher when formula containing 4% rather than 1% 18:3(n - 3) was fed, suggesting that 1% 18:3(n - 3) may limit tissue (n - 3) fatty acid accretion. These results suggest that future studies of essential fatty acid requirements, specifically 18:3(n - 3), should consider possible influences on the saturated fatty acids which also play a functional role in tissue structural lipids.

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Nonessential fatty acids in formula fat blends influence essential fatty acid metabolism and composition in plasma and organ lipid classes in piglets.

The n-6 and n-3 fatty acid status of developing organs is the cumulative result of the diet lipid composition and many complex events of lipid metabolism. Little information is available, however, on the potential effects of the saturated fatty acid chain length (8:0-16:0) or oleic acid (18:1) content of the diet on the subsequent metabolism of the essential fatty acids 18:2n-6 and 18:3n-3 and their elongated/desaturated products. The effects of feeding piglets formulas with fat blends containing either coconut oil (12:0 + 14:0) or medium chain triglycerides (MCT, 8:0 + 10:0) but similar levels of 18:1, 18:2n-6 and 18:3n-3, or MCT with high or low 18:1 but constant 18:2n-6 and 18:3n-3 on the fatty acid composition of plasma, liver and kidney triglycerides, phospholipids and cholesteryl esters, and of brain total lipid, were studied. Diet-induced changes in the fatty acid composition of lipid classes were generally similar for plasma, liver and kidney. Dietary 18:1 content was reflected in tissue lipids and was inversely associated with levels of 18:2n-6. Lower percentage of 18:2n-6, however, was not associated with lower levels of its elongated/desaturated product 20:4n-6 but was associated with higher levels of 22:6n-3. Feeding coconut oil vs. MCT resulted in lower 18:1 levels in all lipids, and higher percentages of 20:4n-6 in tissue phospholipid. Increasing the dietary n-6/n-3 ratio from 5 to 8 significantly increased tissue percentage of 18:2n-6 and decreased phospholipid 22:6n-3.(ABSTRACT TRUNCATED AT 250 WORDS)

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Docosahexaenoic acid in developing brain and retina of piglets fed high or low alpha-linolenate formula with and without fish oil.

Docosahexaenoic acid (22:6n-3) can be synthesized in the liver and/or brain from alpha-linolenic acid (18:3n-3) and is required in large amounts in structural membranes of developing brain and retina. The adequacy and efficacy of formulas containing 18:3n-3 and/or fish oil in providing 22:6n-3 for deposition was investigated in piglets fed formula from birth to 15 days. The test formulas contained high (HL) or low (LL) 18:3n-3 (3.9 or 0.7% of the total formula fatty acids, respectively), or low 18:3n-3 plus fish oil (LL+FO) to provide C20 and C22 n-3 polyunsaturated fatty acids (0.8% of total fatty acids). Fatty acid analyses of synaptic plasma membrane and retina ethanolamine phospholipids (EPL), which are especially enriched in 22:6n-3, were compared to those of 15-day-old piglets fed sow milk (SM). Feeding LL resulted in lower 22:6n-3 in synaptic plasma membrane. Fatty acid levels in HL and LL+FO piglets were equivalent to SM, with the exception of lower 22:5n-3 in the synaptic plasma membrane of LL+FO and in the retina of HL and LL+FO-fed piglets. Levels of 22:4n-6 were also lower in the retina of the LL+FO group. The results suggest formula 18:3n-3 is at least 24% as effective as C20 and C22 n-3 fatty acids as a source of membrane 22:6n-3. This study shows dietary 18:3n-3, as the only n-3 fatty acid, can support deposition of comparable percentage of 22:6n-3 to natural milk. Fish oil also supported tissue levels of 22:6n-3 similar to natural milk; however, lower 22:4n-6 may indicate possible inhibitory effects on n-6 metabolism.

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n-3 fatty acid requirements of the newborn.

Whether docosahexaenoic acid (22:6n-3) is an essential nutrient for term or preterm infants, or if not, the quantity of dietary linolenic acid (18:3n-3) needed to support sufficient synthesis of 22:6n-3 for assimilation in the central nervous system is unknown. Infants fed formulas have lower plasma and red blood cell (RBC) levels of 22:6n-3 than breast fed infants. No relationship between the intake of 18:3n-3 in formula (0.8 or 4.5% of fatty acids, 18:2n-6/18:3n-3 ratio 35:1 or 7:1, respectively) and the infant's RBC 22:6n-3 was found. Premature infants (< 33 wk gestation) also showed a decrease in RBC 22:6n-3 during feeding with formula containing 18:3n-3 as the only n-3 fatty acid. However, a marked decrease in plasma and RBC 22:6n-3 occurred between premature birth and the start of full enteral feeding at 1-2 wk of age. This was not reversed by breast milk or formula feeding. Piglets, which are appropriate for studies of infant lipid metabolism, had decreased brain synaptic plasma membrane, retina and liver 22:6n-3 and increased 22:5n-6 when fed formula with 0.8% fatty acids (0.3% of kcal) as 18:3n-3. Formula with 4.0% fatty acids (1.7% of kcal) as 18:3n-3 resulted in similar accretion of 22:6n-3 in the organs compared to milk fed animals. The studies suggest the dietary requirement for 18:3n-3 in term animals in energy balance exceeds 0.3% diet kcal.(ABSTRACT TRUNCATED AT 250 WORDS)

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Plasma and red blood cell fatty acid values as indexes of essential fatty acids in the developing organs of infants fed with milk or formulas.

The dietary requirement of n-6 and n-3 fatty acids for normal biochemical and functional development of the central nervous system (CNS) is an important, unresolved issue in infant nutrition. High levels of arachidonic acid (AA; 20:4n-6) and docosahexaenoic acid (DHA; 22:6n-3) are found in the CNS and are important to normal learning and visual function. Dietary fatty acids may be desaturated and elongated to AA and DHA, respectively, but may also be oxidized for energy. Synthesis of AA and DHA in the young infant, therefore, depends on adequate desaturase enzyme activity, as well as an adequate supply of dietary 18:2n-6, 18:3n-3, and energy. Levels of AA and DHA are lower in the plasma and red blood cell (RBC) lipids of infants fed formula rather than human milk and are not increased with increased formula 18:2n-6 or 18:3n-3 supply. The decline in AA and DHA in infants fed formula becomes evident in the order plasma phospholipid greater than RBC phosphatidylcholine greater than RBC phosphatidylethanolamine. As in infants, piglets fed formula rather than natural milk have lower plasma and RBC AA and DHA concentrations. Despite lower levels in the plasma and RBC, analyses of CNS lipids demonstrated adequate AA and DHA in piglets fed formula with greater than 7% kcal 18:2n-6 and greater than 0.3% kcal 18:3n-3. This finding suggests that circulating lipid fatty acids are not specific indexes of organ deficiency. The rapid decrease in circulating lipid AA and DHA concentrations experienced by premature infants during early postnatal parenteral and enteral nutrition, however, may be related to oxidation of 18:2n-6 and 18:3n-3, rather than equilibrium of circulating lipids with the dietary fatty acids. Arachidonic acid and DHA may be conditionally essential nutrients for these infants because of oxidation of 18:2n-6 and 18:3n-3 for energy during periods of negative energy balance.

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