M. T. Clandinin

Intrauterine fatty acid accretion rates in human brain: implications for fatty acid requirements

Fatty acid components of infant brain were determined to assess fatty acid requirements for synthesis of structural lipids in brain tissue during the last trimester of development in the fetus. Quantitative fatty acid analysis of cerebellum, frontal and occipital brain lobes indicated rapid accretion of chain elongation and desaturation products during the last trimester of brain growth. Frontal and occipital brain lobes were similar in fatty acid content. Fatty acid accretion rates were determined by regression analysis of tissue fat components at varying gestational ages. Tissue accretion of saturated and omega-9 fatty acids, as well as total fatty acid content, paralleled increases in whole brain weight. Levels of linoleic (C18:2, omega-6) and linolenic (C18:3, omega-3) acids were consistently low in brain during the last trimester of development, while marked substantial accretion of long chain desaturation products, arachidonic (C20:4, omega-6) and docosahexaenoic (C22:6, omega-3) acids occurred. Accretion of individual fatty acids of cerebellum also reflected changes in tissue total fatty acid content, with exception of the levels of C18:3, omega-3 and its chain elongation products present in cerebellum during the last trimester. These developmental changes and estimates of fatty acid incorporation into whole brain and cerebellum are quantitatively relevant to estimation of fatty acid requirements of the low birth weight neonate.

Extrauterine fatty acid accretion in infant brain: implications for fatty acid requirements

Total fatty acid content of infant brain was determined to assess minimal fatty acid requirements for synthesis of structural lipids in brain tissue during the first 13 weeks of life. Fatty acid accretion rates were determined by regression analysis of tissue fat components at varying postnatal ages. Quantitative fatty acid analysis indicated that postnatal accretion of long-chain polyenoic fatty acids in cerebellum, frontal and occipital brain lobes initially appeared to lag behind the rate of increase in brain weight and brain fat content. After a 4-week period total long-chain fatty acids increased at a rate similar to the increase in brain weight. Accretion of individual fatty acids in cerebellum also reflected changes in tissue total fatty acid content. These developmental changes in fatty acid components of whole brain and cerebellum are quantitatively relevant to estimation of the minimal extrauterine fatty acid requirements of the human neonate.

Dietary fat: exogenous determination of membrane structure and cell function.

Evidence indicates that principal features of the membrane involve structural organization of lipids in the form of a bilayer with functional proteins either bound to the bilayer surface or inserted into the bilayer and interacting within specific domains in the lipid milieux. In homeotherms, intrinsic and extrinsic factors apparently form the basis for determination of membrane lipid composition and thus membrane physicochemical properties. Moreover, many intrinsic metabolic controls, such as fatty acid desaturation and phospholipid biosynthesis, may be attenuated by change in the nature of the extrinsic or dietary influence. This review will focus on the role of dietary fat as a determinant of subcellular structural constituents to illustrate that feeding nutritionally adequate diets differing in fatty acid composition can induce physiological transitions in membrane function involving the activity of enzymes responsible for synthesis of membrane constituents, hormone‐activated functions and expression of activity in the cell nucleus.—Clandinin, M. T.; Cheema, S.; Field, C. J., Garg, M. L., Venkatraman, J., Clandinin, T. R. Dietary fat: exogenous determination of membrane structure and cell function. FASEB J. 5: 2761‐2769; 1991.

Lower proportion of CD45R0+ cells and deficient interleukin-10 production by formula-fed infants, compared with human-fed, is corrected with supplementation of long-chain polyunsaturated fatty acids.

Background The immune consequences of adding 20:4n-6 and 22:6n-3 fatty acids to preterm infant formula are not known. Methods The effect of feeding preterm infants (14–42 days of age) human milk (Human Milk group), infant formula (Formula group), or formula with added long-chain polyunsaturated fatty acids 20:4n-6 and 22:6n-3 (Formula + LCP group) on isolated peripheral blood lymphocytes (by flow cytometry) and lipid composition (by gas–liquid chromatography) was determined. Lymphocytes were stimulated in vitro with phytohemagglutinin to measure soluble interleukin (sIL)-2R and IL-10 production (by enzyme-linked immunosorbent assay). Results With age, the percentage of CD3+CD4+ T cells and the percentage of CD20+ cells increased in the Human Milk and Formula + LCP groups (P < 0.05), but not in the unsupplemented Formula group. Compared with the Formula group, CD4+ cells from the Formula + LCP and Human Milk groups expressed more CD45R0 (antigen mature) and less CD45RA (antigen naive) at 42 days of age (P < 0.05). At 42 days, IL-10 production was lower (P < 0.05) in cells of the Formula group than in cells of the Human Milk group. Production of IL-10 by the cells of the Formula + LCP group was not different from that produced by the Human Milk group cells. An age-related decrease (P < 0.05) in sIL-2R production by Formula + LCP lymphocytes was observed, but sIL-2R production at 42 days in the Formula + LCP group did not differ significantly from that in the Human Milk group. Compared with Formula alone, adding LCP to formula resulted in a lower C18:2n-6 and higher C20:4n-6 content in lymphocyte phospholipids (P < 0.05). Conclusions Adding LCP to a preterm infant formula resulted in lymphocyte populations, phospholipid composition, cytokine production, and antigen maturity that are more consistent with that in human milk–fed infants. This may affect the ability of the infant to respond to immune challenges.

Requirements of Newborn Infants for Long Chain Polyunsaturated Fatty Acids

Interest in infant feeding has focused on energy, protein, essential fatty acids, and specific minerals. Biological advantages of feeding human milk versus proprietary formulas have been examined, with particular attention being accorded to the appropriateness of human milk for the premature infant and to the need to optimize the nutrient balance provided in semisynthetic formulations. The present paper will focus on the requirements for very long chain polyunsaturated essential fatty acids (Cz0 and CZ2), excluding considerations of fatty acid utilization for energy metabolism, to assess the basis of current knowledge concerning the infant’s requirements for essential fatty acids. Metabolism of long chain polyunsaturated fatty acids derived from C18:zw6 and C I R : ~ ~ , ) ~ by chain elongation-desaturation (Fig. 1 ) is essential for synthesis of complex structural lipids and prostaglandins. In homeothermic animals these essential fatty acids are required for normal function in developing tissues and appropriate maturation of a wide variety of physiological processes (reviewed by 1). During development, fetal accretion of long chain metabolites of 0 6 and 0 3 fatty acids may result from maternal or placental synthesis and transfer, or alternatively, the fetus may be capable of metabolizing C18:2w6 and CIS: 3,,,3 to longer chain homologues (2). After birth the infant must synthesize the very long chain polyunsaturated fatty acids (LCPE) derived from CI8 , 2 ~ 6 and C18: 3w3 or be fed these fatty acids as they are normal constituents of most membranes.

Intravenous Fish Oil Emulsion Attenuates Total Parenteral Nutrition-Induced Cholestasis in Newborn Piglets

Total parenteral nutrition (TPN) causes intrahepatic cholestasis and membrane phospholipid changes. Fatty acid (FA) composition of bile and hepatocyte phospholipid is influenced by dietary FA composition. We hypothesized that altering FA composition of i.v. lipid emulsions modifies 1) severity of TPN-induced cholestasis; 2) hepatocyte membrane composition and function; 3) bile flow and composition. Newborn piglets received either sows milk, TPN with i.v. soybean oil or TPN with i.v. fish oil (FO). After 3 wk, basal and stimulated bile flow were measured after bolus injections of 20, 50, and 100 µmol/kg of taurocholate (TCA). Bile was analyzed for bile acids, cholesterol, phospholipids, and phospholipid-FA. Sinusoidal and canalicular membrane PL-FA, fluidity, and Na+/K+-ATPase were measured. Although the soybean oil-fed animals developed cholestasis, the FO and milk group had similar liver and serum bilirubin. Basal and stimulated bile flow rates were impaired in the soybean oil but not in the FO group. Hepatocyte membrane FA composition reflected dietary FA. Changes in sinusoidal and canalicular membrane fluidity and sinusoidal Na+/K+-ATPase activity did not explain the effect of FO on TPN-induced cholestasis. Intravenous FO reduces TPN-induced cholestasis by unknown mechanisms.

Vitamin A and E content of human milk at early stages of lactation

The influence of gestational age and lactational stage on carotene, retinol ester, alpha-tocopherol and gamma-tocopherol content of early human milk was studied. These nutrients were analyzed simultaneously using normal phase high-performance liquid chromatography. Serial samples of colostrum and early milk representative of complete early morning expressions were obtained during the first 6 weeks post-partum from mothers giving birth prematurely (PT) and at term (FT). Colostrum carotene content declined significantly during the first week of lactation. There was no apparent gestational age effect on milk carotene levels. The longitudinal pattern of change observed for milk retinol ester and alpha-tocopherol content was however, significantly different between PT and FT milk. Retinol ester levels were similar on days 1-2 postpartum reaching a maximal level on days 3-4 postpartum in FT milk. For PT milk the maximum retinol ester concentration occurred on days 6-7 postpartum. Retinol ester content decreased throughout lactation. The rate of decline was more marked for FT milk. The concentration of alpha-tocopherol in colostrum was higher in FT milk. On all subsequent days examined the level of alpha-tocopherol was greater in PT milk. For both FT and PT milk the alpha-tocopherol concentration was higher during the first week of lactation when compared with following weeks. gamma-Tocopherol levels were not influenced by gestational age or lactational stage. Levels of milk vitamin A and E did not appear to correlate with maternal intake. Colostrum levels of vitamin A and E may imply active sequestration by the mammary gland in compensation for limited placental transport. Early milk content of vitamin A and E appears to parallel mammary gland lipid synthesis.

Brain development and assessing the supply of polyunsaturated fatty acid.

Membrane lipids are necessary for structure and function of the developing nervous system. Rapid synthesis of brain tissue occurs during the last trimester of development of the human brain and the early postnatal weeks. This synthesis of brain structure involves the formation of complex lipids, many of which contain significant quantities of chain-elongated desaturated homologs of essential fatty acids. The present report discusses the implications of change in nutritional status on processes of brain development and metabolic events that involve lipids.

Modulation of adipose tissue fat composition by diet: A review

Fatty acid composition of human adipose tissue is not consistent. Factors such as, sample site, age, sex, disease state and genetics, have minor influence in the fatty acid composition of adipose tissue. Dietary fatty acid intake appears to be a dominant determinant of the level of essential and non-essential fatty acids present in human adipose tissue triglycerides. Diet fat composition also appears to influence adipose tissue membrane fatty acid composition and thus may alter the structure and functional properties of the adipocyte membrane.

Differential effects of dietary linoleic and α-linolenic acid on lipid metabolism in rat tissues

Comparative effects of feeding dietary linoleic (safflower oil) and α-linolenic (linseed oil) acids on the cholesterol content and fatty acid composition of plasma, liver, heart and epididymal fat pads of rats were examined. Animals fed hydrogenated beef tallow were used as isocaloric controls. Plasma cholesterol concentration was lower and the cholesterol level in liver increased in animals fed the safflower oil diet. Feeding the linseed oil diet was more effective in lowering plasma cholesterol content and did not result in cholesterol accumulation in the liver. The cholesterol concentration in heart and the epididymal fat pad was not affected by the type of dietary fatty acid fed. Arachidonic acid content of plasma lipids was significantly elevated in animals fed the safflower oil diet and remained unchanged by feeding the linseed oil diet, when compared with the isocaloric control animals fed hydrogenated beef tallow. Arachidonic acid content of liver and heart lipids was lower in animals fed diets containing safflower oil or linseed oil. Replacement of 50% of the safflower oil in the diet with linseed oil increased α-linolenic, docosapentaenoic and docosahexaenoic acids in plasma, liver, heart and epididymal fat pad lipids. These results suggest that dietary 18∶2ω6 shifts cholesterol from plasma to liver pools followed by redistribution of 20∶4ω6 from tissue to plasma pools. This redistribution pattern was not apparent when 18∶3ω3 was included in the diet.