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Biomedical subjects

S C Cunnane

Publications and source records attributed to S C Cunnane.

At least 55 records · Page 3Linked to original sources
PubMed1996

Accumulation of polyunsaturates is decreased by weight-cycling: whole-body analysis in young, growing rats.

Whole-body fatty acid analysis in rats has previously shown that 50-70% of dietary linoleate and alpha-linolenate is beta-oxidized to CO2 and that this value increases with refeeding after a single episode of fasting. Our hypothesis was that repeated fasting-refeeding or weight-cycling would increase the beta-oxidation of linoleate and alpha-linolenate thereby depleting their whole-body levels. In rats consuming 3% energy as linoleate and 0.15% energy as alpha-linolenate during a 16 d balance period, 19% of the linoleate consumed accumulated in weight-cycled rats compared with 34% in the free-fed controls (P < 0.01). Similarly, 11% of the alpha-linolenate consumed accumulated in the weight-cycled rats compared with 22% in the controls (P < 0.01). Arachidonate and docosahexaenoate also accumulated to lower extents in the weight-cycled rats than in the controls. In contrast, whole-body accumulation of palmitate, stearate and oleate was not different between the weight-cycled group and the controls when measured as a proportion of intake or relative to weight gain. Thus, whole-body depletion of linoleate and alpha-linolenate did not occur per se but the partitioning of linoleate and alpha-linolenate was significantly altered by weight-cycling resulting in lower whole-body accumulation and higher apparent oxidation of all polyunsaturates especially linoleate and alpha-linolenate.

Animals↗
PubMed1996

Effects of n-3 fatty acids on the NMR profile of plasma lipoproteins.

The effects of fish oil supplementation (14.5 g n-3 fatty acids/day) on plasma lipoprotein particles in healthy volunteers were assessed by high resolution 13C and 1H nuclear magnetic resonance (NMR) spectroscopy. Resonances not previously observed in the 13C and 1H spectra of plasma and isolated lipoproteins were detected after fish oil ingestion. The 13C resonances, centered at 14.3, 127.1, and 131.6 ppm, have been assigned to specific carbon groups (CH3-CH2-CH = CH-, CH3-CH2-CH = CH-CH2-, CH3-CH2-CH = CH-CH2-, respectively) in eicosapentaenoic acid (C20:5n-3) and docosahexaenoic (C22:6n-3) DHA. The new lipid resonance observed in the 1H spectra of plasma (0.941 ppm) is consistent with the incorporation of these n-3 fatty acids into lipoprotein particles. The presence of increased EPA and DHA in plasma lipids was confirmed by gas-liquid chromatography. A marked reduction in the intensity of the methylene signal from very low density lipoproteins (VLDL) was also observed with fish oil. This reduction arises from a decrease in plasma triglyceride concentration (ca. 18%) and a reduction in the number of VLDL particles. Transverse relaxation studies of isolated VLDL and low density lipoprotein (LDL) showed significant elevation in the T2 of the -(CH2)n- and CH3- signals from non-n-3 fatty acids. The relaxation characteristics and signal intensity of the novel 1H peak (0.941 ppm) point to the existence of n-3 enriched microenvironments within lipoprotein particles. These findings suggest that incorporation of EPA and DHA into VLDL and LDL, after fish oil ingestion, leads to significant alteration in the molecular architecture of lipoprotein particles.

Adult↗
PubMed1996

The Canadian Society for Nutritional Sciences 1995 Young Scientist Award Lecture. Recent studies on the synthesis, beta-oxidation, and deficiency of linoleate and alpha-linolenate: are essential fatty acids more aptly named indispensable or conditionally dispensable fatty acids?

Recent research on the synthesis, beta-oxidation, and deficiency of linoleate and alpha-linolenate raises questions about whether the term essential fatty acid is outdated. Linoleate and alpha-linolenate can be synthesized from their respective 16-carbon precursors, which are present in the human diet; whether the rate of conversion and dietary supply of the precursors are sufficient depends on the actual requirement for linoleate and alpha-linolenate. Pure deficiency of linoleate (diet excluding linoleate but including alpha-linolenate and oleate) has not been studied until recently, so it is unclear whether the recommended linoleate intake at 2% of energy, as based on classical essential fatty acid deficiency studies, is appropriate or too high. Despite marked whole-body depletion of linoleate and poor conservation of linoleate stores, pure linoleate deficiency has little effect on growth in rats, suggesting its requirement may be less than 2% of energy. Whole-body fatty acid balance studies indicate that the main route of linoleate and alpha-linolenate metabolism is oxidation, which increases sufficiently that accumulation of dietary linoleate and alpha-linolenate may actually be prevented in undernutrition and fasting refeeding. Part of the oxidized carbon from linoleate and alpha-linolenate is recycled and used for de novo synthesis of "non-essential" fatty acids and cholesterol, which in the brain of the suckling rat, can exceed conversion to longer chain polyunsaturates by as much as 10- to 40-fold. Given the capability to synthesize linoleate and alpha-linolenate, the imprecise knowledge of true linoleate requirement, and the absence of clear symptoms of their deficiency in healthy adults, it might be advantageous to consider using the terms indispensable and conditionally dispensable to clarify the conditional nature of the dietary requirement for linoleate and alpha-linolenate.

Animals↗
PubMed1996

13C NMR spectroscopy and gas chromatograph--combustion--isotope ratio mass spectrometry: complementary applications in monitoring the metabolism of 13C-labelled polyunsaturated fatty acids.

This review aims to describe some recent and novel applications of stable isotope tracer technology to study the metabolism of 13C-polyunsaturated fatty acids. Stable isotope methodology has existed for several decades, and in that sense, it is not novel per se. However, in the past 10 years, developments in the fields of isotope ratio mass spectrometry, nuclear magnetic resonance (NMR) spectroscopy, and biological approaches to labelling tracer compounds with stable isotopes have provided new opportunities in fatty acid research. Sample preparation for isotope ratio mass spectrometry has been converted from a manual combustion method to an on-line or continuous flow method, making it much more versatile and easier to use. Similarly, 13C-NMR spectroscopy has recently developed as a remarkably useful method for monitoring metabolic steps and pathways both in vivo and at the molecular level. Coincident with these improvements in instrumentation, the commercial availability of numerous uniformly 13C-labelled compounds has made these studies more affordable. The application of some of these developments to questions in the field of polyunsaturated fatty acid metabolism is described.

Animals↗
PubMed1995

Fasting/refeeding has little lasting effect on long-chain fatty acids accumulating in the developing rat conceptus.

The objective of this study was to delineate the influence of maternal fasting-refeeding on accumulation of long-chain fatty acids by the developing conceptus in chow-fed pregnant rats. At term, the rat conceptus normally accumulates < 5% of total maternal whole body n - 6 polyunsaturates and < 15% of whole body n - 3 polyunsaturates. In contrast to the ad libitum-fed controls, the conceptus of fasted-refed rats was the main site of accumulation of n - 6 and n - 3 polyunsaturates since the maternal carcass (excluding liver) actually had a lower content of polyunsaturates at the end of the fasting-refeeding period than at the start. The rise in the content of triacylglycerols in the conceptus during fasting was specifically attributable to increased arachidonate, docosatetraenoate and docosahexaenoate; all changes in conceptus triacylglycerols were back to ad libitum control values by the end of the refeeding period (term). Conversely, although conceptus total phospholipids did not change significantly during fasting-refeeding, there was a net increase in the phospholipid content of both palmitate and oleate in conceptus after refeeding. We conclude that the developing rat conceptus is largely resistant to the marked changes in maternal fatty acid intake and retention that occur during fasting and refeeding.

Animals↗
PubMed1995

Utilization of carbon from dietary polyunsaturates for brain cholesterol synthesis during early postnatal development in the rat: a 13C NMR study.

Incorporation of 13C from a dietary precursor into cholesterol was studied in neonatal rats. Rats were given uniformly 13C-enriched polyunsaturated fatty acids intragastrically and total lipid extracts of liver and brain were analyzed by 13C-NMR 1, 4, 8, and 15 days later. 13C-enrichment was detected in brain but not in liver cholesterol. Maximal 13C-labeling was observed 4 days after injection of the label. Spectra revealed that 70% of newly incorporated 13C had 13C as an adjacent neighbor, the other 30% had 12C as the neighbor. Double quantum NMR revealed the arrangement in the cholesterol skeleton of the 13C-13C pairs transferred from precursors to cholesterol. Desmosterol, an intermediate of cholesterol synthesis, was identified in the spectra of brain lipids. Comparison of 13C-13C unit arrangements in both cholesterol and desmosterol allowed carbons 26 and 27 of desmosterol to be unambiguously assigned.

Animals↗
PubMed1995

Effect of tumor necrosis factor-alpha on triglyceride and phospholipid content and fatty acid composition of liver and carcass in rats.

We have previously shown that a continuous infusion of tumor necrosis factor-alpha (TNF-alpha) in rats results in an increase in plasma triglyceride (TG), liver protein and DNA, and at the same time a reduction in muscle protein. However, there is no information on the associated effects of TNF-alpha on liver and muscle lipids. The present study, therefore, determined the effect of TNF-alpha on the TG and phospholipid (PL) content and their fatty acid composition, in the liver and carcass of rats and correlated with the plasma levels of insulin, corticosterone, and catecholamines. Total parenteral nutrition that met the daily nutrient requirements was continuously infused for 10 d through a central vein catheter in two groups of rats, one receiving infused TNF-alpha (100 micrograms/kg/d) and a control group. Hepatic TG and PL, expressed either as mg/g dry weight or total organ content, were significantly increased in the TNF-alpha-infused group compared with controls. Livers of TNF-alpha infused rats contained significantly less saturated and monounsaturated fatty acids and significantly more polyunsaturated fatty acids (PUFA) of the omega 3 and omega 6 series than controls. The carcass, on the other hand, contained significantly more monounsaturated and significantly less polyunsaturated fatty acids of the omega 6 series than controls. There were no changes in corticosterone level. Although plasma glucose levels were comparable between control and TNF-alpha infused rats, the latter had a marked increase in insulin levels, demonstrating insulin resistance. In addition TNF-alpha infused rats had raised norepinephrine levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Synthesis of linoleate and alpha-linolenate by chain elongation in the rat.

The objective was to determine whether rats could synthesize longer chain polyunsaturates from hexadecadienoate (16:2n-6) and hexadecatrienoate (16:3n-3). Rats were gavaged with uniformly 13C-labelled hexadecadienoate or hexadecatrienoate, euthanized 24 h later, and total lipids were extracted from liver and carcass. Gas chromatography/combustion/isotope ratio mass spectrometry was used to measure 13C levels in individual liver, carcass, and whole body fatty acids. 13C Enrichment was present in desaturated and chain-elongated polyunsaturates, including linoleate, arachidonate, alpha-linolenate, and docosahexaenoate at 12-13% of the dose of tracer given. 13C Enrichment from hexadecatrienoate was highest in carcass and liver alpha-linolenate, representing 3.5 and 17.9% of the total alpha-linolenate pool, respectively. For linoleate, arachidonate, or docosahexaenoate, the contribution of 13C did not exceed 0.2% of the total body pool. Green leafy vegetables common in the human diet were shown to contain up to 1.2% of total fatty acids as hexadecadienoate and 11.6% as hexadecatrienoate. Hence, humans consuming green vegetables probably synthesize a small proportion of their total body content of linoleate and alpha-linolenate.

Animals↗
PubMed1995

Effect of nibbling versus gorging on cardiovascular risk factors: serum uric acid and blood lipids.

Nibbling has been reported to decrease serum cholesterol under fasting conditions, as well as the incidence of cardiovascular disease. It has been suggested that these effects are partly attributable to reduced concentrations of serum insulin, which are also observed. However, data on the effects of nibbling on serum lipids throughout the day are not available, nor is it known how nibbling affects serum uric acid as a further insulin-related risk factor for cardiovascular disease. We have attempted to address these issues. Seven healthy men consumed identical diets in a randomized crossover design either as three meals daily (control) or as 17 meals daily (nibbling) for 2 weeks. On day 13, serum lipid levels were measured over the course of the day (12 hours) together with the 24-hour urinary excretion of mevalonic acid as an indicator of hepatic cholesterol synthesis. Concentrations of uric acid in serum and 24-hour urinary excretion of uric acid were also determined. Mean (+/- SE) percent treatment differences in day-long total, low-density lipoprotein (LDL), and non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein (apo) B were significant, with lower values on the nibbling diet as compared with the control diet (8.1% +/- 1.6%, P = .002; 12.2% +/- 2.6%, P = .005; 10.1% +/- 1.6%, P < .001; and 9.9% +/- 2.6%, P = .008, respectively). No significant difference was seen in the total to HDL cholesterol ratio or in urinary mevalonic acid excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Nutritional attributes of traditional flaxseed in healthy young adults.

The objective was to determine the influence of consuming 50 g flaxseed/d for 4 wk on several indexes of nutrition in young healthy adults. During flaxseed consumption, alpha-linolenate was increased significantly in adipose tissue, and n-3 polyunsaturates were increased in plasma lipids. Plasma LDL cholesterol was also reduced by up to 8%, and total urinary lignan excretion was increased more than fivefold (P < 0.05). Muffins containing 25 g flaxseed did not differ significantly from control muffins in their content of thiobarbituric acid-reactive substances, and alpha-linolenate in the muffins was not significantly reduced by baking. Antioxidant vitamins and lipid hydroperoxides in plasma were not significantly affected by flaxseed consumption. Bowel movements per week increased by 30% while flaxseed was consumed (P < 0.05). We conclude that traditional flaxseed has modest beneficial effects on several indexes of nutritional status without compromising antioxidant status.

Adipose Tissue↗
PubMed1995

Propionate inhibits incorporation of colonic [1,2-13C]acetate into plasma lipids in humans.

Acetate and propionate, produced during colonic fermentation of unabsorbed carbohydrate, may influence systemic lipid metabolism. As a preliminary study to see whether colonic acetate is incorporated into plasma lipids and whether propionate inhibits this process, 5 healthy males were studied after fasting overnight. They were given, in random order, 12.5 mmol (1.05 g) [1,2-13C]sodium acetate by intravenous or rectal infusion, and the rectal infusion was given with or without 6 mmol (0.58 g) sodium propionate. Two hours after rectal acetate, 13C recoveries in plasma cholesterol (0.59 +/- 0.22%) and triglycerides (1.24 +/- 0.69%) were significantly greater than after intravenous acetate (0.09 +/- 0.12% and 0.29 +/- 0.18%, respectively). Addition of propionate reduced 13C recovery in triglycerides (0.19 +/- 0.06%, P = 0.024) compared with rectal acetate alone, but the effect on cholesterol (0.26 +/- 0.05%) was not significant. These data suggest that incorporation of colonic acetate into plasma triglycerides is inhibited by propionate. Further studies are required to quantify the effects of colonic acetate and propionate on lipid synthesis.

Acetates↗
PubMed1995

Similar distribution of trans fatty acid isomers in partially hydrogenated vegetable oils and adipose tissue of Canadians.

The objective of this study was to evaluate the composition of trans fatty acids in the subcutaneous fat of Canadians relative to the composition of dietary sources of trans fatty acids. The fatty acid composition, total trans acid content, and the geometric and positional isomer distribution of unsaturated fatty acids of subcutaneous adipose tissue of Canadians were determined using a combination of capillary gas-liquid chromatography and silver nitrate thin-layer chromatography. The mean total trans fatty acid content was 6.80% at the abdominal site and 5.80% at the lateral thigh site. Total trans isomers of linoleic acid (18:2n-6) were present at 1.17% in abdominal and 1.59% in thigh adipose tissue, with 9c.12t-18:2 being the most prevalent isomer followed by 9c-13t-18:2 and 9t,12c,-18:2. The oleic acid (18:1) trans isomer distribution in adipose tissue differed from that in butter fat, but it was similar to that in partially hydrogenated vegetable oils. The reverse was true for the 18:1 cis isomers. Total 18:1 trans isomers were inversely related to 18:2n-6 content in adipose tissue, suggesting the trans fatty acid intake is inversely related to the intake of linoleic acid. Partially hydrogenated vegetable oils appear to be the major source of trans fatty acids in adipose tissue of Canadians.

Adipose Tissue↗
PubMed1995

Zinc deficiency impairs whole-body accumulation of polyunsaturates and increases the utilization of [1-14C]linoleate for de novo lipid synthesis in pregnant rats.

Zinc deficiency impairs the metabolism of polyunsaturates, but the degree to which its effects are independent of food intake are still in question. Identical amounts of a semiliquid control diet (26.4 mg zinc/kg) or moderately zinc deficient diet (3.2 mg zinc/kg) were tube fed to rats for 11 days during the second half of pregnancy to evaluate the specific effects of zinc deficiency on maternal utilization and fetal accumulation of polyunsaturates. The whole body fatty acid balance method was used to determine net accumulation of polyunsaturates and their whole-body disappearance. Incorporation of 14C from [1-14C]linoleate into maternal and fetal lipid classes was also studied on days 20-21. At term, zinc-deficient rats had significantly higher whole-body disappearance of linoleate and alpha-linolenate and lower accumulation of n-6 and n-3 long-chain polyunsaturates. Zinc-deficient rats had higher 14C activity in free cholesterol, saturates, and monounsaturates in several maternal organs but not in the fetuses. We conclude that during pregnancy, moderate zinc deficiency not affecting food intake or weight gain still alters whole-body metabolism of linoleate and alpha-linolenate towards increased beta-oxidation and also increases the utilization of carbon from linoleate for de novo lipid synthesis.

Adipose Tissue↗
PubMed1995

Moderate, selective depletion of linoleate and alpha-linolenate in weight-cycled rats.

In rats, the response of adipose tissue composition to a single weight cycle (24-48 h of fasting followed by refeeding) is characterized by a decrease primarily in linoleate and alpha-linolenate, with little or no change in other fatty acids. We tested the hypothesis that during successive weight cycles caused by repeated fasting and refeeding, the depletion of linoleate and alpha-linolenate from whole body stores would be exacerbated despite their adequate availability during the refeeding period. Four complete weight cycles (24-h fasting followed by 72-h ad libitum refeeding) induced a significant quantitative decrease in total n-3 and n-6 polyunsaturates, particularly linoleate and alpha-linolenate, and a simultaneous increase in the accumulation of palmitate, palmitoleate, and oleate in carcass total lipids and in perirenal and epididymal adipose tissue. A significant positive relationship was observed between the increasing ratio of saturates+monounsaturates to n-3 + n-6 polyunsaturates in adipose tissue and the number of weight cycles (r = +0.96, P < 0.0001). The percentage of linoleate and alpha-linolenate in adipose tissue was inversely related to the number of weight cycles. We conclude that, despite providing adequate n-6 and n-3 polyunsaturates in the diet during the refeeding period, weight cycling in young growing rats causes a moderate, selective depletion of linoleate and alpha-linolenate from tissue stores.

Adipose Tissue↗
PubMed1994

Application of the balance method to determining accumulation, metabolism, and apparent oxidation of linoleic and alpha-linolenic acids in the pregnant rat.

Pregnancy-induced changes in whole-body partitioning of linoleic acid (18:2n-6) and alpha-linolenic acid (18:3n-3) between accumulation, conversion to longer-chain polyunsaturates (LCP), and disappearance (apparent oxidation) were determined over a 13-day balance period. 18:2n-6, 18:3n-3 and n-6 and n-3 LCP levels were measured in food, feces, organs, and carcass. Accumulation was estimated on the basis of paired difference values between one group killed at the beginning and one at the end of the balance period. Actual whole-body accumulation of 18:2n-6 and 18:3n-3 (mg per rat) was similar in pregnant and nonpregnant rats, but when expressed as milligrams per gram weight gain, it was greater in nonpregnant rats. Net accumulation of n-6 and n-3 LCP was significantly greater in pregnant rats whether expressed as milligrams per rat or as milligrams per gram body weight gain. Apparent oxidation of 18:2n-6 and 18:3n-3 expressed as a percentage of intake was similar in both groups, but when expressed as milligrams per gram weight gained, it was significantly greater in the nonpregnant group. We conclude that the balance method provides a useful index of whole-body and organ partitioning of 18:2n-6 and 18:3n-3. This method demonstrates that despite the higher accumulation of LCP during pregnancy, significantly more 18:2n-6 and 18:3n-3 is apparently oxidized than is converted to their respective LCP.

Animals↗