Biomedical subjects

S C Cunnane

Publications and source records attributed to S C Cunnane.

At least 19 recordsLinked to original sources

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↗

PubMed1992

Early postnatal development in the rat is characterized by accumulation of highly unsaturated triacylglycerols.

Our objective was to determine the quantitative changes of individual triacylglycerol (TG) species in liver and carcass during early postnatal growth. Pregnant rats were killed at d 21 of pregnancy, and neonatal rats were killed at d 3 or 9 after birth. Quantitative changes in fatty acids and TG species of fetal/neonatal liver and carcass were determined using capillary gas liquid chromatography. At postnatal d 3 or 9 compared with fetal d 21, total carcass TG increased 11- to 12-fold, with nonessential fatty acids increasing 8- to 9-fold, n-6 essential fatty acids (EFA) increasing 34- to 44-fold, and n-3 EFA increasing 19- to 29-fold, respectively. Total neonatal liver TG increased 13-fold from fetal d 21 to postnatal d 3, with a 6-fold increase in non-EFA, a 34-fold increase in total n-6 EFA and a 65-fold increase in total n-3 EFA. At postnatal d 3 compared with fetal d 21, larger molecular weight liver TG classes (C56-C64) increased 68-fold, followed by lower molecular weight TG classes C40-C48 (19-fold) with only a 6-fold increase in C50-C54. In liver, highly unsaturated TG classes (C56-C64) accounted for 49% of total TG at postnatal d 3 and consisted mainly of arachidonic, docosahexaenoic, and linoleic acids accompanied by palmitic and oleic acids. During early postnatal development, TG species containing one, two, or even three 20-22 EFA may be structurally important themselves or serve as direct substrates for synthesis of phospholipids.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Short-term energy deficit causes net accumulation of linoleoyl-enriched triacylglycerols in rat liver.

Energy depletion by reduced food intake over 4 days resulted in a 73% reduction in total rat liver triacylglycerols (TG). In liver TG of energy-depleted rats, dilinoleoyl oleoyl glycerol (OLL) and trilinoleoyl glycerol (LLL) were quantitatively increased by 85% and 147%, respectively. The net increase in linoleoyl-enriched species could be quantitatively accounted for by the release of linoleate from monolinoleoyl species and its subsequent reacylation into dilinoleoyl species and trilinolein during energy depletion. Hence while palmitate, oleate and some linoleate are being hydrolyzed, presumably for oxidation, some linoleate is retained and contributes to the remodelling of hepatic triacylglycerols during energy deficit.

Animals↗

PubMed1991

Specific types of colonic fermentation may raise low-density-lipoprotein-cholesterol concentrations.

To assess the effects of increased colonic fermentation on serum lipids, eight healthy volunteers were placed on two identical 2-wk metabolic diets, one of which was supplemented with lactulose (18-25 g/d). Lactulose raised day-long concentrations of breath hydrogen and serum glutamine as indicators of increased colonic fermentation by 78 +/- 13% (P less than 0.001) and 24.7 +/- 9.5% (P less than 0.05), respectively). Unexpectedly, however, fasting serum total and low-density-lipoprotein cholesterol and apolipoprotein B concentrations were higher at 2 wk by 8.9 +/- 1.5% (P less than 0.001), 10.9 +/- 2.2% (P less than 0.005), and 18.9 +/- 5.9% (P less than 0.02), respectively, compared with the control diet. With lactulose, mean free fatty acid concentrations were reduced over the day by 19.5 +/- 5.9% (P less than 0.02), with no change in mean day-long blood glucose, serum insulin, or C-peptide concentrations. We conclude that certain rapidly fermented substrates may raise rather than lower serum lipids, possibly through increasing the amount of acetate absorbed from the colon.

Acetates↗

PubMed1990

Differential utilization of long chain fatty acids during fasting-induced triacylglycerol depletion. III. Comparison of n-3 and n-6 fatty acids in rat plasma and liver.

Previous research has shown that arachidonic acid (20:4(n-6)) is preferentially retained in liver triacylglycerol in fasted compared to fed rats consuming a diet containing n-6 fatty acids. It was hypothesized that eicosapentaenoic (20:5(n-3)) and docosahexaneoic acids (22:6(n-3)) would be similarly retained in liver and plasma triacylglycerol of fasted rats consuming a diet containing n-3 fatty acids. In comparison with fed rats, it was observed that in partially fasted rats consuming diets which contained 5% sunflower oil (78% 18:2(n-6)) or 5% marine fish oil (30% 20:5(n-3) and 22:6(n-3)), both liver and plasma had significantly depleted triacylglycerol levels containing higher proportions of both arachidonic and docosahexaneoic acids but a lower proportion of eicosapentaenoic acid (marine fish oil group only). Separation of liver and plasma triacylglycerol by silicic acid column chromatography and silver nitrate TLC showed that the majority of long chain fatty acids utilized during fasting were derived from the triacylglycerol subclasses containing palmitic acid (16:0), palmitoleic acid (16:1(n-7)) and oleic acid (18:1(n-9)) with retention o both highly saturated and polyunsaturated subclasses. Greater utilization of eicosapentaenoic acid than either arachidonic acid or docosahexaenoic acid during fasting may be due to triacylglycerol speciation of the former with readily oxidized monounsaturated fatty acids.

Animals↗

PubMed1990

Intussusception in the Syrian golden hamster.

Of a series of ninety-six young male Syrian Golden hamsters, 13% developed lethargy, anorexia, diarrhoea and colocolic intussusception when their diet was changed from a basal laboratory-grade rodent chow to a nutritionally complete semi-purified diet. Histologically, the colon of the hamsters with intussusception had markedly reduced mucus production. Plasma levels of gastric inhibitory polypeptide (GIP) were reduced 80% (P less than 0.01) but peptide tyrosine/tyrosine and enteroglucagon in plasma were increased 290 and 526% respectively in hamsters with intussusception. Variations in dietary fatty acid composition had no effect but intussusception was not observed after changing the dietary carbohydrate from sucrose to starch.

Animals↗

PubMed1990

Long-chain fatty acid composition of maternal liver lipids during pregnancy and lactation in the rat: comparison of triglyceride to phospholipid.

The change in long-chain fatty acid composition in maternal liver was studied during pregnancy and lactation in the rat. Maternal liver triglycerides and phospholipids transiently accumulated and were depleted of long-chain fatty acids during pregnancy and lactation. During pregnancy, maternal liver accumulated triglyceride, but triglyceride fatty acid composition changed little. However, maternal liver total phospholipid fatty acid composition changed significantly without a change in the total pool size throughout pregnancy or lactation. The change in composition of (n-3) and (n-6) essential fatty acids in maternal liver triglyceride and total phospholipid occurred in an apparently dyssynchronous manner throughout pregnancy and lactation.

Animals↗

PubMed1990

Release of essential fatty acids from the rat mesenteric vascular bed perfused in vitro: modulation by zinc.

The rat mesenteric vascular bed releases prostaglandins when perfused in vitro. The present study evaluated the effect of perfusion of the rat mesenteric vascular bed in vitro with a buffer containing 0, 3, 6, or 9 nM of added zinc on the release of essential fatty acids over a 150-min period. Long chain fatty acids in the mesenteric lipids and in total lipid of the perfusion effluent were assayed by gas liquid chromatography. The presence of 6 nM zinc in the perfusing buffer almost completely prevented the change in 16-22 carbon long chain fatty acids in the mesenteric phospholipids and decreased the release of free fatty acids in comparison to that occurring in the absence of additional zinc. The results suggest that physiological amounts of zinc in the perfusion medium reduce the release of essential fatty acid from rat mesenteric lipids.

Animals↗

PubMed1990

Metabolic effects of reducing rate of glucose ingestion by single bolus versus continuous sipping.

Modifying the rate of absorption has been proposed as a therapeutic principle of specific relevance to diabetes. To demonstrate clearly the metabolic benefits that might result from reducing the rate of nutrient delivery, nine healthy volunteers took 50 g glucose in 700 ml water on two occasions: over 5-10 min (bolus) and at a constant rate over 3.5 h (sipping). Despite similar 4-h blood glucose areas, large reductions were seen in serum insulin (54 +/- 10%, P less than 0.001) and C-peptide (47 +/- 12%, P less than 0.01) areas after sipping, together with lower gastric inhibitory polypeptide and enteroglucagon levels and urinary catecholamine output. There was also prolonged suppression of plasma glucagon, growth hormone, and free-fatty acid (FFA) levels after sipping, whereas these levels rose 3-4 h after the glucose bolus. An intravenous glucose tolerance test at 4 h demonstrated a 48 +/- 10% (P less than 0.01) more rapid decline in blood glucose (Kg) after sipping than after the bolus. Furthermore, FFA and total branched-chain amino acid levels as additional markers of insulin action were lower over this period despite similar absolute levels of insulin and C-peptide. These findings indicate that prolonging the rate of glucose absorption enhances insulin economy and glucose disposal.

Administration, Oral↗

PubMed1989

Nibbling versus gorging: metabolic advantages of increased meal frequency.

We studied the effect of increasing the frequency of meals on serum lipid concentrations and carbohydrate tolerance in normal subjects. Seven men were assigned in random order to two metabolically identical diets. One diet consisted of 17 snacks per day (the nibbling diet), and the other of three meals per day (the three-meal diet); each diet was followed for two weeks. As compared with the three-meal diet, the nibbling diet reduced fasting serum concentrations of total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B by a mean (+/- SE) of 8.5 +/- 2.5 percent (P less than 0.02), 13.5 +/- 3.4 percent (P less than 0.01), and 15.1 +/- 5.7 percent (P less than 0.05), respectively. Although the mean blood glucose level and serum concentrations of free fatty acids, 3-hydroxybutyrate, and triglyceride were similar during both diets, during the nibbling diet the mean serum insulin level decreased by 27.9 +/- 6.3 percent (P less than 0.01) and the mean 24-hour urinary C-peptide output decreased by 20.2 +/- 5.6 percent (P less than 0.02). In addition, the mean 24-hour urinary cortisol excretion was lower by 17.3 +/- 5.9 percent (P less than 0.05) at the end of the nibbling diet than at the end of the three-meal diet. The blood glucose, serum insulin, and C-peptide responses to a standardized breakfast and the results of an intravenous glucose-tolerance test conducted at the end of each diet were similar. We conclude that in addition to the amount and type of food eaten, the frequency of meals may be an important determinant of fasting serum lipid levels, possibly in relation to changes in insulin secretion.

3-Hydroxybutyric Acid↗

PubMed1989

Modulation of long chain fatty acid unsaturation by dietary copper.

Research over the past 20 years into the effect of copper on fatty acid profiles in several species suggests that copper has a unique effect on long chain fatty acid metabolism. Copper supplementation in the pig and rat and copper deficiency in the rat, mouse and human indicates that inadequate copper intake (or genetic copper deficiency in the brindled mouse and in Menke's disease) impairs the ability to monounsaturate long chain saturated fatty acids and that, conversely, copper supplementation (greater than 150 mg/kg diet) usually increases monounsaturated fatty acids. Several recent studies of copper deficiency in the rat suggest that our interpretation of these effects needs to be more refined since membrane fatty acid profiles do not appear as sensitive to the effects of copper depletion as triglyceride fatty acid profiles. This suggests that changes in long chain fatty acid metabolism other than desaturation may also be affected by copper.

Animals↗

PubMed1989

Essential fatty acid and lipid profiles in plasma and erythrocytes in patients with multiple sclerosis.

This study was conducted to investigate the possible differences in erythrocyte lipid composition, which might account for the previously reported increase in erythrocyte membrane zinc levels in patients with multiple sclerosis (MS). Compared with healthy control subjects, plasma lipids in patients with MS contained less sphingomyelin but more phosphatidylserine and the cholesterol-phospholipid ratio was 42% higher in the plasma from MS patients (p less than 0.01). In erythrocytes from MS patients, phosphatidylinositol was lower and erythrocyte cholesterol per milligram protein was significantly lower than concentrations in healthy control subjects (p less than 0.01). Among the long-chain fatty acids, the omega-3 fatty acids were lower in plasma from MS patients and linoleic acid was lower in erythrocyte ghosts from MS patients (p less than 0.01). We conclude that altered levels of cholesterol in plasma and erythrocytes from MS patients may contribute to increased erythrocyte-membrane Zn in MS patients. It cannot be stated with certainty whether the altered fatty acid profiles in MS patients were a function of the disease or of altered fatty acid intake.

Cholesterol↗

PubMed1988

Differential utilization of long chain fatty acids during triacylglycerol depletion. I. Rat heart after ischemic perfusion.

Rat hearts were perfused with Krebs-Henseleit buffer for 90 min according to the Langendorff procedure. Normoxic perfusion for 90 min resulted in minor changes in fatty acid composition and a decrease in residual heart triacylglycerol to 60% of preperfusion values. When the protocol included 30 min of slow perfusion-induced ischemia, the hearts were observed to be depleted of 89% of their initial triacylglycerol content. The triacylglycerol fatty acid composition (mg %) remained similar after compared to before perfusion except for a 121 mg % increase in stearic acid and a 225 mg % increase in arachidonic acid. The percentage composition of both fatty acids was significantly inversely correlated with the amount of triacylglycerol remaining in the heart after perfusion. Postperfusion, arachidonic acid and stearic acids were present at nearly 1:1 in the residual heart triacylglycerol, suggesting that a common mechanism may be involved in the selective retention of these fatty acids by the heart.

Animals↗