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Biomedical subjects

S C Cunnane

Publications and source records attributed to S C Cunnane.

At least 73 records · Page 4Linked to original sources
PubMed1994

Utilization of uniformly labeled 13C-polyunsaturated fatty acids in the synthesis of long-chain fatty acids and cholesterol accumulating in the neonatal rat brain.

Polyunsaturated fatty acids are needed for normal neonatal brain development, but the degree of conversion of the 18-carbon polyunsaturated fatty acid precursors consumed in the diet to their respective 20- and 22-carbon polyunsaturates accumulating in the brain is not well known. In the present study, in vivo 13C nuclear magnetic resonance spectroscopy was used to monitor noninvasively the brain uptake and metabolism of a mixture of uniformly 13C-enriched 16- and 18-carbon polyunsaturated fatty acid methyl esters injected intragastrically into neonatal rats. In vivo NMR spectra of the rat brain at postnatal days 10 and 17 had larger fatty acid signals than in uninjected controls, but changes in levels of individual fatty acids could not be distinguished. One day after injection of the U-13C-polyunsaturated fatty acid mixture, 13C enrichment (measured by isotope ratio mass spectrometry) was similar in brain phospholipids, free fatty acids, free cholesterol, and brain aqueous extract; 13C enrichment remained high in the phospholipids and cholesterol for 15 days. 13C enrichment was similar in the main fatty acids of the brain within 1 day of injection but 15 days later had declined in all except arachidonic acid while continuing to increase in docosahexaenoic acid. These changes in 13C enrichment in brain fatty acids paralleled the developmental changes in brain fatty acid composition. We conclude that, in the neonatal rat brain, dietary 16- and 18-carbon polyunsaturates are not only elongated and desaturated but are also utilized for de novo synthesis of long-chain saturated and monounsaturated fatty acids and cholesterol.

Aging↗
PubMed1994

Comparison of amino acid v peptide based enteral diets in active Crohn's disease: clinical and nutritional outcome.

Elemental diets are considered an effective primary treatment for active Crohn's disease. This study examined the hypothesis that improvement occurs because of the presence of amino acids or the low fat content, or both. A randomised, controlled trial was undertaken in 40 patients with active Crohn's disease to evaluate clinical and nutritional outcomes after an amino acid based diet containing 3% fat was given by a feeding tube compared with a peptide based diet containing 33% fat. After three weeks' treatment, clinical remission occurred in 84% of patients who were given the amino acid diet and 75% of patients who received the peptide diet (p = 0.38). Plasma linoleic acid concentration was reduced after the amino acid but not the peptide diet. An increase in total body nitrogen was associated with the magnitude of nutritional depletion before treatment and at six months' follow up, only patients who showed gains in total body nitrogen after enteral nutrition had a sustained clinical remission. This study shows that peptide based high fat diets are as effective as amino acid low fat diets for achieving clinical remission in active Crohn's disease. Improved total body protein stores but not essential fatty acid depletion may be an important indicator of a sustained remission.

Adult↗
PubMed1994

Quantitative measurements of dietary and [1-14C]linoleate metabolism in pregnant rats: specific influence of moderate zinc depletion independent of food intake.

Our objective was to investigate whether the effects of moderate zinc deficiency on metabolism of linoleate during pregnancy could be distinguished from the effects of low food intake. Rats were force-fed an isoenergetic zinc-deficient (3.2 mg/kg) or control (26.4 mg/kg) semiliquid diet during the second half of pregnancy. Fatty acid quantity and composition in both maternal and fetal organs were analyzed at term. Recovery of 14C in lipid- and water-soluble metabolites from orally injected [1-(14)C]linoleate was also studied. After 10 days of gavaging identical amounts of the diet, zinc-deficient rats had lower serum zinc and lower uterus and placenta weights than controls, but body weights were similar. At term, zinc-deficient rats had a fatty acid composition in organs and carcass similar to that of the controls, but the zinc-deficient fetuses had lower long-chain n-6 and n-3 polyunsaturates in brain, liver, and carcasses. Lipids extracted from most organs of zinc-deficient rats contained lower 14C levels, but 14C was raised in the maternal carcass lipids and in water-soluble metabolites. We conclude that zinc deficiency during pregnancy increases oxidation of linoleate and decreases synthesis or transport of polyunsaturates to the fetuses and that these effects are independent of depressed food intake, i.e., they are specific to zinc depletion. Thus, zinc deficiency has distinct effects on fatty acid metabolism, which are readily observed using 14C tracer methods.

Animals↗
PubMed1993

Detection of [U-13C]eicosapentaenoic acid in rat liver lipids using 13C nuclear magnetic resonance spectroscopy.

Fatty acid carbons are well-resolved in 13C nuclear magnetic resonance (NMR) spectra of lipid extracts, but application of this methodology to the metabolism of 13C-labelled fatty acids has not yet been reported. In the present study, 13C NMR was used to monitor the presence of 98% [U-13C]eicosapentaenoic acid (EPA) in liver and carcass lipids 24 h after it had been injected into the stomach of a rat. Natural abundance 13C NMR spectra of liver total fatty acid extracts were obtained from four control rats for comparison. At 24 h post-injection, quantitative high resolution 13C NMR showed 13C enrichment in liver fatty acid extracts was present mainly at olefinic and at the n-1 to n-4 carbons, but 13C signal intensities for C-1 to C-4 of [U-13C]EPA were markedly reduced or absent. Small 13C resonances, possibly indicative of some 13C incorporation into docosahexaenoic acid and saturated or monounsaturated fatty acids, were present in spectra of liver fatty acids. Liver and carcass fatty acid composition was similar in both the controls and the EPA-injected rat, suggesting little accumulation of the injected [U-13C]EPA after 24 h. We conclude that the carbon-specific data provided by 13C NMR of lipid extracts may be useful in monitoring the fate of individual carbons during tracer studies using 13C-labelled fatty acids.

Animals↗
PubMed1993

Refeeding after fasting increases apparent oxidation of N-3 and N-6 fatty acids in pregnant rats.

The intake, excretion, and accumulation of long-chain fatty acids was analyzed to test the hypothesis that during pregnancy in the rat whole-body partitioning of n-6 and n-3 fatty acids between net accumulation or disappearance (apparent oxidation) is determined by both maternal energy status and fetal development. From midpregnancy to term in ad libitum-fed rats consuming-rodent chow, 30% more saturates and monounsaturates accumulated in the whole body than were consumed, whereas 28% of dietary n-6 fatty acids and 55% of dietary n-3 fatty acids were apparently oxidized. After 48 hours of fasting during midpregnancy (days 13 to 15) followed by refeeding to term, net accumulation of saturates and monounsaturates was equivalent to intake, but whole-body disappearance of n-6 fatty acids exceeded intake by 6% (NS), whereas n-3 fatty acid disappearance exceeded intake by 43%. Thus during refeeding after fasting, dietary n-6 and n-3 fatty acids were apparently completely oxidized and there was actually a net loss of n-3 fatty acids from whole-body stores. Fasting during midpregnancy did not significantly affect fetal weight gain or maternal gestational hyperlipidemia toward term. We conclude that during pregnancy n-6 and n-3 fatty acids are not only required for maternal and fetal structural and storage lipids, but are also used to meet energy requirements, especially during refeeding after fasting.

Animals↗
PubMed1993

High alpha-linolenic acid flaxseed (Linum usitatissimum): some nutritional properties in humans.

Although high alpha-linolenic acid flaxseed (Linum usitatissimum) is one of the richest dietary sources of alpha-linolenic acid and is also a good source of soluble fibre mucilage, it is relatively unstudied in human nutrition. Healthy female volunteers consumed 50 g ground, raw flaxseed/d for 4 weeks which provided 12-13% of energy intake (24-25 g/100 g total fat). Flaxseed raised alpha-linolenic acid and long-chain n-3 fatty acids in both plasma and erythrocyte lipids, as well as raising urinary thiocyanate excretion 2.2-fold. Flaxseed also lowered serum total cholesterol by 9% and low-density-lipoprotein-cholesterol by 18%. Changes in plasma alpha-linolenic acid were equivalent when 12 g alpha-linolenic acid/d was provided as raw flaxseed flour (50 g/d) or flaxseed oil (20 g/d) suggesting high bioavailability of alpha-linolenic acid from ground flaxseed. Test meals containing 50 g carbohydrate from flaxseed or 25 g flaxseed mucilage each significantly decreased postprandial blood glucose responses by 27%. Malondialdehyde levels in muffins containing 15 g flaxseed oil or flour/kg were similar to those in wheat-flour muffins. Cyanogenic glycosides (linamarin, linustatin, neolinustatin) were highest in extracted flaxseed mucilage but were not detected in baked muffins containing 150 g flaxseed/kg. We conclude that up to 50 g high-alpha-linolenic acid flaxseed/d is palatable, safe and may be nutritionally beneficial in humans by raising n-3 fatty acids in plasma and erythrocytes and by decreasing postprandial glucose responses.

Blood Glucose↗
PubMed1993

Childhood origins of lifestyle-related risk factors for coronary heart disease in adulthood.

Research over the past 40 years clearly points to childhood as a critical period when dietary and lifestyle patterns are initiated which have longterm implications for coronary heart disease risk in adult life. Smoking, high habitual dietary intake of total fat and saturated fat, low exercise level, and excessive alcohol consumption often occur in family aggregates. They are correlated with elevated serum cholesterol, obesity, and hypertension in children, as well as with a predisposition to premature death from coronary heart disease. Intervention studies in children and adolescents show, however, that these lifestyle-risk factors are controllable through education and dietary counselling of the affected individual and their family. Equally important are the emerging data in adults showing that vigorous longterm intervention involving reduction of dietary fat and work-related stress, increased exercise, and elimination of smoking all contribute to a significant improvement in coronary perfusion. Hence, effective dietary and lifestyle management of coronary heart disease can occur at early or later stages of the disease and needs better support from health authorities at the national and international level.

Adolescent↗
PubMed1993

The importance of energy and nutrient supply in human brain evolution.

Current evolutionary theories do not adequately address the question of how the human brain evolved to be larger and more sophisticated than that of other primates. The human brain/body weight ratio is 4-5 times higher than in primates and, relative to the rest of the body, requires up to 10 times as much energy as in other land-based mammals. Human brain evolution must therefore have required a stable food supply providing a reliable source of both high dietary energy and a cluster of 'brain-specific' nutrients over a long period of time. These nutrient and energy requirements are available in the marine and shore-based food chain but are difficult if not impossible to obtain in the terrestrial food chain. We suggest that marine and estuarine ecosystems provided hominids with the appropriate stimulus to develop a relatively large brain. This occurred in conjunction with the evolution of other uniquely human features, particularly relative hairlessness, bipedalism and abundant neonatal subcutaneous fat. Invertebrates, molluscs, small or slow-moving fish, and marine algae would have provided a stable, abundant supply of energy, long chain polyunsaturates and other nutrients essential for the brain and would have done so with comparatively little mammalian competition. The land-water interface would thus have allowed the hominid brain to develop sufficient neurological complexity to enable sophisticated tool and behaviour patterns to evolve in humans as a natural sequel to such a biochemical and environmental stimulus.

Animals↗
PubMed1992

Gestational hyperlipidemia in the rat is characterized by accumulation of n - 6 and n - 3 fatty acids, especially docosahexaenoic acid.

We have evaluated the relative and quantitative changes in long-chain fatty acids in maternal liver, serum, carcass and conceptus (fetuses plus placentae) during pregnancy in the rat, to ascertain whether previous concern over lower proportions of n - 6 and n - 3 fatty acids in maternal serum could be indicative of suboptimal n - 6 or n - 3 fatty acid status. Gestational hyperlipidemia was characterized by proportional decreases in linoleic, stearic and arachidonic acids but increases in palmitic and docosahexaenoic acids. However, the quantitative amount (microgram/ml) of linoleic, arachidonic and docosahexaenoic acids in serum lipids actually increased 2-5-fold from mid-pregnancy to term. Compared to non-pregnant rats, gestational hyperlipidemia was also associated with a lower proportion but similar quantity of linoleic acid in maternal carcass and adipose stores. We conclude that gestational hyperlipidemia in the rat is characterized by a relative but not quantitative decrease in whole-body stores of n - 6 fatty acids and a marked proportional and quantitative increase in docosahexaenoic acid in maternal organs and in the conceptus.

Adipose Tissue↗
PubMed1992

Carbon-by-carbon discrimination of 13C incorporation into liver fatty acids.

Quantitative carbon-by-carbon analysis would be useful in determining the origin and fate of carbons involved in fatty acid metabolism. Incorporation of 13C from 2-[13C]acetate into specific carbons of liver fatty acids was lowest at the n-2 carbon of saturates and monoenes but was 47% greater at acyl C1 than at C2, suggesting substantial redistribution of the 13C from C2 to C1 of acetyl CoA or malonyl CoA prior to 13C incorporation into fatty acids during de novo synthesis or during elongation. Thus, 13C derived from exogenous acetate can be quantitatively measured and is differentially incorporated into individual carbons depending on position in the fatty acid molecule.

Animals↗
PubMed1992

Linoleoyl-enriched triacylglycerol species increase in maternal liver during late pregnancy in the rat.

In view of the previously reported changes in the fatty acid composition of maternal liver triacylglycerols in late pregnancy, changes in the composition of maternal liver triacylglycerol species were assessed in rats fed a semi-purified diet during pregnancy. Between day 18 and day 21 of pregnancy, total maternal liver triacylglycerols increased by 50%. Triacylglycerol species with a total acyl carbon number (C) of 50 or 60 (C50, C60) remained unchanged while C48 and C52-C58 were relatively increased. The individual triacylglycerol species containing one, two or three linoleoyl moieties were incompletely recovered using a polar high temperature gas-liquid chromatography (GLC) column. Nevertheless, at day 21 compared to day 18, the linoleoyl-containing species were relatively increased by 62-463%, while tripalmitin was decreased by 38%. Our data suggest that despite an adequate intake of linoleic acid (25 g/kg in the diet), maternal hepatic triacylglycerol content of linoleic acid decreased during mid-pregnancy but increased significantly toward term possibly in preparation for the transfer of linoleic acid to the neonate during lactation.

Aging↗
PubMed1992

Quantitative changes in long-chain fatty acids during fetal and early postnatal development in rats.

The quantitative importance of triacylglycerol as a source of total essential fatty acids during early postnatal development is reported in the accompanying article. Our objective here was to measure the quantitative changes in individual long-chain fatty acids in specific lipid classes of the carcass, liver, and brain of the developing rat mainly to describe the relative accumulation of long-chain vs. precursor fatty acids. Fatty acids in carcass phosphatidylcholine (micrograms/g) were lower at fetal days 18-21 than at either fetal day 15 or postnatal days +3 to +9. Individual long-chain fatty acids in liver phosphatidylcholine and phosphatidylethanolamine increased markedly by day +3 postnatally, whereas in brain phosphatidylethanolamine, the postnatal increase was delayed to between days +6 and +9. Fatty acids in carcass and liver triacylglycerols increased quantitatively by 10- to 300-fold from fetal day 21 to postnatal day +3 with amounts of both arachidonic and docosahexaenoic acid equaling linoleic acid. The ratios of linoleic and alpha-linolenic acids to respective long-chain products were significantly higher in triacylglycerols, whereas that of stearic to oleic acid was higher in phospholipids. We conclude that, during early postnatal life, oleic, linoleic, and alpha-linolenic acids are required in quantitatively greater amounts in triacylglycerols, whereas stearic acid and long-chain essential fatty acids are required in phospholipids.

Animals↗
PubMed1992

Triacylglycerol: an important pool of essential fatty acids during early postnatal development in rats.

Developmental changes in the content and composition of major organ lipid pools are not well known. Our objective was to assess quantitatively the changes in lipids, particularly those containing long-chain fatty acids, in the placenta and the brain, liver, and carcass of the fetal and suckling rat. Pregnant dams were killed at days 15, 18, and 21 (term) of pregnancy and the placentas and fetuses removed and analyzed; suckling rats were killed at days +3, +6, and +9 of lactation. Whereas the long-chain fatty acid content of the phospholipids (mg/g) of the fetal or suckling rat remained relatively constant from day 18 of pregnancy to day +9 of lactation, long-chain fatty acids in triacylglycerols increased from prenatal values by 10- to 12-fold during the first 9 postnatal days. Prenatally, triacylglycerol accounted for no more than 32% of total whole body essential fatty acids (day 21), but postnatally this increased to 81-88%. From day 21 to day +9, the proportion of n-6 and n-3 essential fatty acids within the total triacylglycerol pool of the suckling rat increased 71 and 317%, respectively. We conclude that in the suckling rat, triacylglycerol is quantitatively the most important source of essential fatty acids during at least the first 9 days of life.

Animals↗
PubMed1992

Preferential retention of linoleic acid-enriched triacylglycerols in liver and serum during fasting.

Fasting has been reported to quantitatively increase linoleic and arachidonic acids in liver triacylglycerols, but the origin and mechanism of this change are unknown. The changes in long-chain fatty acids and triacylglycerol species of liver, serum, adipose tissue, and heart were therefore examined during a period of 24- or 48-h fasting in the rat. In liver and serum triacylglycerols, fasting resulted in a quantitative increase in arachidonic, stearic, linoleic, alpha-linolenic, and docosahexaenoic acids but a decrease in oleic, palmitic, and palmitoleic acids. After fasting, oleic acid was depleted the most from liver and serum triacylglycerols followed by palmitoleic and palmitic acids. Triacylglycerol species containing palmitic, palmitoleic, and oleic acids were depleted the most from liver and serum during fasting. Linoleic acid-enriched triacylglycerol species were proportionally and, in some cases, quantitatively increased in liver and serum triacylglycerols during fasting. Net retention of triacylglycerol species with a total acyl carbon number of 56 or 58 in the liver and 60 in serum was also observed during fasting. Selective retention of triacylglycerol species did not occur in the heart or perirenal or epididymal adipose tissue during fasting. Tissue phospholipid fatty acids were largely unaffected by fasting. Our data suggest that during fasting, long-chain fatty acids released from adipose tissue are differentially utilized and hepatic triacylglycerol species are remodeled, permitting optimal tissue composition of essential fatty acids, particularly linoleic acid.

Adipose Tissue↗