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S C Cunnane

Publications and source records attributed to S C Cunnane.

At least 91 records · Page 5Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Differential utilization of long chain fatty acids during triacylglycerol depletion. II. Rat liver after starvation.

Rats starved for 96 hr were shown to have a 94% reduction in liver triacylglycerol. Among the long chain fatty acids in liver triacylglycerol, only stearic acid and arachidonic acid were proportionally increased (2.5 and 6 times, respectively); palmitic and linoleic acids were unchanged, and palmitoleic and oleic acids were proportionally decreased. Stearic and arachidonic acids (mg%) were correlated positively within the triacylglycerol fraction, and both fatty acids varied inversely with total triacylglycerol (mg/g) in fed and starved rats. The utilization of long chain fatty acids from liver triacylglycerol during starvation resulted in selective retention of arachidonic acid and stearic acid and suggests that differential hydrolysis of liver triacylglycerol by hepatic lipase may occur or selective reacylation of these specific fatty acids may occur during starvation.

Animals↗

Effects of low magnesium diet on the vascular prostaglandin and fatty acid metabolism in rats.

Deficiency of magnesium with cardiovascular effects is thought to be related to alterations in the biosynthesis of prostaglandins (PGs) in the vasculature. Measurements were made of the PGE2, 6-keto-PGF1 alpha and thromboxane B2 (TxB2) outflow from the perfused isolated mesenteric arterial bed and the fatty acid composition of the tissue in rats maintained for 14 weeks on a low magnesium (LMg) diet. The serum Mg levels were significantly decreased and the serum Ca levels were significantly increased in the LMg group as compared to the controls. The arachidonic acid concentration in the triacylglyceride fraction was significantly increased in the LMg group. Long chain polyunsaturates such as 22:4n6 and 22:6n3 were consistently increased in the LMg rats as compared to the controls in both the phospholipid and triglyceride fractions as previously reported in other tissues. The PGE2, 6-keto-PGF1 alpha and TxB2 outflows were significantly increased in the LMg group as compared to the controls. These findings suggest that the biosynthesis of eicosanoids, mainly PGI2, is stimulated in Mg deficiency, and this may provide protection against intracellular Mg depletion and Ca accumulation, so as to counteract to the constricted and hyperreactive state of the vasculature in such a condition.

Animals↗

Copper intake affects rat heart performance during ischemia-reperfusion: possible relation to altered lipid and fatty acid metabolism.

Hearts from rats fed low copper (1.3 mg copper/kg diet) or a copper-supplemented diet (243 mg copper/kg diet) were perfused for 90 min according to the Langendorff method. The perfusion protocol included 30 min normoxia, 30 min ischemia and 30 min reperfusion. After 90 min perfusion, hearts from the low copper group had gained more weight, had lower coronary perfusion pressure, developed less force of contraction and secreted less 6-keto PGF1 alpha into the perfusate than hearts from the copper-supplemented group. After perfusion, the major lipid change in the hearts from both groups was a 85-90% decrease in total triacylglycerol. In both groups, stearic acid and arachidonic acid (mg%) were increased in the triacylglycerol fraction after heart perfusion. The quantitative (mg/g) decrease in the triacylglycerol content of stearic acid and arachidonic acid was significantly less in the copper-supplemented group. After perfusion, dihomo-gamma-linolenic acid (mg/g) was lower in heart phospholipids from the low copper group. Dihomo-gamma-linolenic/arachidonic acid (microgram/mg) was significantly decreased after perfusion only in the hearts from the low copper group. Lipid and fatty acid changes in the hearts of the rats fed low dietary copper may contribute to abnormal heart function in this group.

Animals↗

Evidence that adverse effects of zinc deficiency on essential fatty acid composition in rats are independent of food intake.

1. Young male rats were fed on diets containing 3.4, 36 or 411 mg zinc/kg for 10 weeks in order to determine whether effects of Zn deficiency on plasma and liver essential fatty acid composition could be distinguished from those of reduced protein and energy intake. 2. Fatty acid analysis revealed that a Zn intake of 3.4 mg/kg (plasma Zn 0.80 v. 1.97 mmol/l in controls fed on 36 mg Zn/kg) resulted in a significant increase in the linoleic acid:arachidonic acid ratio in both plasma and liver phospholipids in comparison with rats fed on 36 or 411 mg Zn/kg. 3. Zn supplementation (411 mg/kg) decreased the linoleic acid:arachidonic acid ratio in plasma phosphatidylserine compared with that of the controls. 4. The previously reported increase in arachidonic acid (mol %) in liver triacylglycerol of Zn-deficient rats was shown to be a function of a reduced liver triacylglycerol pool size; quantitatively, triacylglycerol content of arachidonic acid in the liver was not significantly affected by Zn intake.

Animals↗

The profile of long-chain fatty acids in serum phospholipids: a possible indicator of copper status in humans.

In previous reports of experimental copper depletion in humans, it was difficult to reliably demonstrate biochemically that there was Cu depletion. In view of the changes in serum phospholipid fatty acid profiles in Cu-deficient rats, it was considered worthwhile to determine the effect of Cu depletion in humans on serum fatty acid profiles. Serum samples from the Cu-depletion study of Reiser et al were analyzed for phospholipid fatty acid composition. After the participants had been on the low copper diet for 11 wk, serum phospholipids contained 27% less oleic acid, 38% more arachidonic acid, and 94% more docosahexaenoic acid (all p less than 0.01) than samples taken from the same subjects before Cu depletion. These fatty acid changes were of a similar direction and magnitude to those in moderately Cu-depleted rats and may be useful as an index of moderate Cu depletion in humans.

Adult↗