Inhibition of COX-2-mediated eicosanoid production plays a major role in the anti-inflammatory effects of the endocannabinoid N-docosahexaenoylethanolamine (DHEA) in macrophages
Meijerink, J. ; Poland, M.C.R. ; Balvers, M.G.J. ; Plastina, P. ; Lute, C. ; Dwarkasing, J.T. ; Norren, K. van; Witkamp, R.F. - \ 2015
British Journal of Pharmacology 172 (2015)1. - ISSN 0007-1188 - p. 24 - 37.
nitric-oxide synthase - cannabinoid receptor - concise guide - fatty-acids - kappa-b - arrive guidelines - prostaglandin e-2 - fish-oil - anandamide - pharmacology
Background and Purpose N-docosahexaenoylethanolamine (DHEA) is the ethanolamine conjugate of the long-chain polyunsaturated n-3 fatty acid docosahexaenoic (DHA; 22: 6n-3). Its concentration in animal tissues and human plasma increases when diets rich in fish or krill oil are consumed. DHEA displays anti-inflammatory properties in vitro and was found to be released during an inflammatory response in mice. Here, we further examine possible targets involved in the immune-modulating effects of DHEA. Experimental Approach Antagonists for cannabinoid (CB)1 and CB2 receptors and PPAR¿ were used to explore effects of DHEA on NO release by LPS-stimulated RAW264.7 cells. The possible involvement of CB2 receptors was studied by comparing effects in LPS-stimulated peritoneal macrophages obtained from CB2-/- and CB2+/+ mice. Effects on NF-¿B activation were determined using a reporter cell line. To study DHEA effects on COX-2 and lipoxygenase activity, 21 different eicosanoids produced by LPS-stimulated RAW264.7 cells were quantified by LC-MS/MS. Finally, effects on mRNA expression profiles were analysed using gene arrays followed by Ingenuity® Pathways Analysis. Key Results CB1 and CB2 receptors or PPARs were not involved in the effects of DHEA on NO release. NF-¿B and IFN-ß, key elements of the myeloid differentiation primary response protein D88 (MyD88)-dependent and MyD88-independent pathways were not decreased. By contrast, DHEA significantly reduced levels of several COX-2-derived eicosanoids. Gene expression analysis provided support for an effect on COX–2-mediated pathways. Conclusions and Implications Our findings suggest that the anti-inflammatory effects of DHEA in macrophages predominantly take place via inhibition of eicosanoids produced through COX-2.
The endocannabinoid system: an emerging key player in inflammation
Witkamp, R.F. ; Meijerink, J. - \ 2014
Current Opinion in Clinical Nutrition and Metabolic Care 17 (2014)2. - ISSN 1363-1950 - p. 130 - 138.
acid amide hydrolase-1 - cancer cell-lines - cannabinoid receptor - n-acylethanolamines - endogenous cannabinoids - docosahexaenoic acid - signaling pathways - lipid mediator - ppar-gamma - fish-oil
Purpose of review: The purpose of this review is to illustrate the expanding view of the endocannabinoid system (ECS) in relation to its roles in inflammation. Recent findings: According to the formal classification, the ECS consists of two cannabinoid receptors, their endogenous fatty acid-derived ligands, and a number of enzymes involved in their synthesis and breakdown. However, many endogenous congeners of classical endocannabinoids have now been discovered, together with a set of receptors structurally or functionally related to the cannabinoid receptors. Endocannabinoids per se behave ‘promiscuously’ with regard to their receptor interactions. It is increasingly recognized how tightly this expanded ECS is intertwined with key processes involved in inflammation. A continuous dynamic exchange of substrates and metabolites exists between ECS and eicosanoid pathways. Endocannabinoids can also be oxygenated by cyclooxygenase and other enzymes to biologically active ‘hybrid’ structures. Diet is among the main factors determining synthesis and release of endocannabinoids and related mediators. Summary: The complexity of what may be called the ‘endocannabinoidome’ requires approaches that take into account its dynamics and interconnections with other regulatory systems. This endocannabinoidome continues to offer possibilities for prevention and intervention, but multiple target approaches will probably provide the only keys to success.
No effect of n-3 fatty acids on high-sensitivity C-reactive protein after myocardial infarction: The Alpha Omega Trial
Hoogeveen, E.K. ; Geleijnse, J.M. ; Kromhout, D. ; Giltay, E.J. - \ 2014
European Journal of Preventive Cardiology 21 (2014)11. - ISSN 2047-4873 - p. 1429 - 1436.
soluble adhesion molecules - coronary-heart-disease - necrosis-factor-alpha - cardiovascular risk - fish-oil - docosahexaenoic acid - inflammatory markers - serum concentrations - supplementation - men
Background Persistent inflammation plays a role in the pathogenesis of atherosclerosis. n-3 Fatty acids may have anti-inflammatory effects. This study examined the effect of plant-derived alpha-linolenic acid (ALA) and marine n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on high-sensitivity C-reactive protein (hsCRP), a systemic marker of (low-grade) inflammation. Design/Methods A supplementary study in the Alpha Omega Trial: a multicenter, double-blind, randomized, placebo-controlled trial of low-dose n-3 fatty acids. Patients were enrolled from 2002 to 2006 and followed for 40 months. A total of 2425 patients, aged 60–80 years (79% men), with a history of myocardial infarction, were randomly assigned to margarines supplemented with a targeted additional intake of 400¿mg/day EPA and DHA, 2¿g/day ALA, EPA-DHA plus ALA, or placebo for 40 months. Results Patients consumed on average 19.8¿g margarine/day, providing an additional amount of 238¿mg/day EPA with 158¿mg/day DHA, 1.98¿g/day ALA, or both, in the active treatment groups. In the placebo group, the geometric mean hsCRP (95% confidence interval (CI)) was 1.84¿mg/l (95% CI: +1.70 to +2.00) at baseline and 1.98¿mg/l (95% CI: 1.82 to 2.15) after 40 months (p¿
Assessment of inflammatory resilience in healthy subjects using dietary lipid and glucose challenges
Wopereis, S. ; Wolvers, D. ; Erk, M. van; Gribnau, M. ; Kremer, B. ; Dorsten, F.A. van; Boelsma, E. ; Garczarek, U. ; Cnubben, N. ; Frenken, L. ; Logt, P. van der; Hendriks, H.F.J. ; Albers, R. ; Duynhoven, J.P.M. van; Ommen, B. van; Jacobs, D.M. - \ 2013
BMC Medical Genomics 6 (2013). - ISSN 1755-8794 - 16 p.
type-2 diabetic-patients - necrosis-factor-alpha - oxidative stress - endothelial dysfunction - cytokine concentrations - postprandial variations - fatty-acids - obese men - fish-oil - markers
Background Resilience or the ability of our body to cope with daily-life challenges has been proposed as a new definition of health, with restoration of homeostasis as target resultant of various physiological stress responses. Challenge models may thus be a sensitive measure to study the body’s health. The objective of this study was to select a dietary challenge model for the assessment of inflammatory resilience. Meals are a challenge to metabolic homeostasis and are suggested to affect inflammatory pathways, yet data in literature are limited and inconsistent. Method The kinetic responses of three different dietary challenges and a water control challenge were assessed on various metabolic and inflammatory markers in 14 healthy males and females using a full cross-over study design. The dietary challenges included glucose (75 g glucose in 300 ml water), lipids (200 ml whipping cream) and a mix of glucose and lipids (same amounts as above), respectively. Blood samples were collected at baseline and at 0.5, 1, 2, 4, 6, 8 and 10 h after consumption of the treatment products. Inflammation (IFN¿, IL-1ß, IL-6, IL-8, IL-10, IL-12p70, TNF-a CRP, ICAM-1, VCAM-1, SAA, E-selectin, P-selectin, thrombomodulin, leukocytes, neutrophils, lymphocytes) and clinical (e.g. glucose, insulin, triglycerides) markers as well as gene expression in blood cells and plasma oxylipin profiles were measured. Results All three dietary challenges induced changes related to metabolic control such as increases in glucose and insulin after the glucose challenge and increases in triglycerides after the lipid challenge. In addition, differences between the challenges were observed for precursor oxylipins and some downstream metabolites including DiHETrE’s and HODE’s. However, none of the dietary challenges induced an acute inflammatory response, except for a modest increase in circulating leukocyte numbers after the glucose and mix challenges. Furthermore, subtle, yet statistically significant increases in vascular inflammatory markers (sICAM-1 and sVCAM-1) were found after the mix challenge, when compared to the water control challenge. Conclusions This study shows that dietary glucose and lipid challenges did not induce a strong acute inflammatory response in healthy subjects, as quantified by an accurate and broad panel of parameters.
Dietary effects of linseed on fatty acid composition of milk and on liver, adipose and mammary gland metabolism of periparturient dairy cows
Mach Casellas, N. ; Zom, R.L.G. ; Widjaja-Greefkes, H.C.A. ; Wikselaar, P.G. van; Weurding, R.E. ; Goselink, R.M.A. ; Baal, J. van; Smits, M.A. ; Vuuren, A.M. van - \ 2013
Journal of Animal Physiology and Animal Nutrition 97 (2013)Suppl. 1. - ISSN 0931-2439 - p. 89 - 104.
multiparous holstein cows - conjugated linoleic-acid - hepatic gene-expression - set enrichment analysis - prostaglandin secretion - blood metabolites - lipid-metabolism - fed flaxseed - fish-oil - lactation
During the transition period in dairy cows, drastic adaptations within and between key tissues and cell types occur in a coordinated manner to support late gestation, the synthesis of large quantities of milk and metabolic homoeostasis. The start of lactation coincides with an increase of triacylglycerols in the liver, which has been associated with several economically important diseases in dairy cows (i.e. hepatic lipidiosis, mastitis). The polyunsaturated fatty acids have been used to improve liver metabolism and immune function in the mammary gland. Therefore, the effects of dietary linseed supplementation on milk quality and liver, adipose and mammary gland metabolism of periparturient dairy cows were studied in 14 cows that were randomly assigned to control or linseed supplementation. Animals were treated from 3 weeks antepartum until 6 weeks post-partum. Linseed did not modify dry matter intake, but increased milk yield and lactose yield, and decreased milk fat concentration, which coincided with lower proportion of C16 and higher proportions of stearic acid, conjugated linoleic acid and a-linolenic acid in milk fat. Linseed supplementation did not significantly change the expression of key lipid metabolism genes in liver and adipose tissues, except of glucose transporter 2 (GLUT2) in liver, which was increased in cows supplemented with linseed, suggesting that more glucose was secreted and probably available for lactose synthesis compared with cows fed control diet. Large adaptations of transcription occurred in the mammary gland when dairy cows were supplemented with linseed. The main affected functional modules were related to energy metabolism, cell proliferation and remodelling, as well as the immune system response.
Measurement of palmitoylethanolamide and other N-acylethanolamines during physiological and pathological conditions
Balvers, M.G.J. ; Verhoeckx, K.C.M. ; Meijerink, J. ; Wortelboer, H.M. ; Witkamp, R.F. - \ 2013
CNS & Neurological Disorders 12 (2013)1. - ISSN 1871-5273 - p. 26 - 33.
tandem mass-spectrometry - polyunsaturated fatty-acids - human plasma - adipose-tissue - endocannabinoid metabolome - electrospray-ionization - palmitoyl-ethanolamine - quantitative method - rat-brain - fish-oil
Palmitoylethanolamide (PEA) belongs to the N-acyl ethanolamines (NAEs), a group of endogenous compounds involved in a variety of physiological processes, including energy homeostasis and inflammation. This review focuses on the analysis of PEA in plasma and tissues and discusses effects of diet and some pathological processes on PEA levels. Originally isolated from egg yolk, PEA has been detected in a variety of tissues and plasma of different species. The compound is present at relatively high levels compared to other NAEs and now mostly analysed using liquid chromatography coupled to mass spectrometry. PEA plasma concentrations show marked fluctuations during the day. However, concentrations in tissues are likely to be more relevant than those in plasma. Most studies suggest that compared to other NAEs, tissue PEA tissue levels are not influenced by changes in dietary fatty acid composition. Effects of inflammation and disease on PEA tissue levels show differences between different models and studies. Therefore, more research is needed on the endogenous role and tissue kinetics of PEA during disease. The rediscovery of the therapeutic potential of PEA has fuelled research and the development of new pharmaceutical formulations. With regard to this there is a need for better kinetic data and models, preferably also on its tissue disposition. Moreover, it is important to learn more about effects of exogenous PEA on the kinetics of other NAEs (and endocannabinoids) and effects of inhibiting its breakdown using inhibitors of the degrading enzymes fatty acid amide hydrolase or N-acylethanolamine-hydrolyzing acid amidase.
Liquid chromatography–tandem mass spectrometry analysis of free and esterified fatty acid N-acyl ethanolamines in plasma and blood cells
Balvers, M.G.J. ; Wortelboer, H.M. ; Witkamp, R.F. ; Verhoeckx, K.C.M. - \ 2013
Analytical Biochemistry 434 (2013)2. - ISSN 0003-2697 - p. 275 - 283.
rat-brain - endocannabinoid metabolome - endogenous cannabinoids - electrospray-ionization - quantitative method - adipose-tissue - fish-oil - anandamide - acylethanolamines - mediators
The origin of N-acyl ethanolamides (NAEs) in plasma is not well understood, and it is possible that NAEs are present in plasma in esterified form. To test this hypothesis, a new and sensitive liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed and validated for the quantification of arachidonoyl ethanolamide, 2-arachidonoyl glycerol, docosahexaenoyl ethanolamide, dihomo-¿-linolenoyl ethanolamide, oleoyl ethanolamide, palmitoyl ethanolamide, and stearoyl ethanolamide in 100 µl of human plasma using a simple acetonitrile extraction step. Using this method, we determined (i) free and esterified NAE levels in human plasma, (ii) free and esterified NAE levels in plasma of mice fed with diets with different amounts of n-3 fatty acids, and (iii) esterified NAE levels in blood cells. Murine and human plasma extracts contained 20- to 60-fold higher levels of esterified NAEs than free NAEs. Moreover, the effect of dietary n-3 fatty acids on murine free plasma NAE profiles was similar for esterified NAEs. Finally, esterified NAEs were also present in murine blood cells, and their pattern followed the same diet effect as observed for free and esterified NAEs in plasma. Together, these data point to the presence of previously ignored pools of esterified NAEs in plasma and blood cells that correlated well with free NAE levels in plasma.
No effects of n)3 fatty acid supplementation on serum total testosterone levels in older men: the Alpha Omega Trial
Giltay, E.J. ; Geleijnse, J.M. ; Heijboer, A.C. ; Goede, J. de; Oude Griep, L.M. ; Blankenstein, M.A. ; Kromhout, D. - \ 2012
International Journal of Andrology 35 (2012)5. - ISSN 0105-6263 - p. 680 - 687.
prostate-cancer risk - hormone-binding globulin - endogenous sex-hormones - late-onset hypogonadism - coronary-heart-disease - postmenopausal women - metabolic syndrome - linolenic acid - elderly-men - fish-oil
The intake of the n-3 fatty acids alpha-linolenic acid (ALA), acid (EPA) and docosahexaenoic acid (DHA) has been related to testosterone levels in epidemiological analyses. The aim of this study was to assess whether the n-3 fatty acids affects testosterone levels in post-myocardial infarction (MI) patients, who are at risk of testosterone deficiency. In a double-blind, placebo-controlled trial of low-dose supplementation of n-3 fatty acids, we included 1850 male post-MI patients aged 60–80 years who participated in the Alpha Omega Trial. Patients were randomly allocated to margarines that provided 400 mg/day of EPA–DHA (n = 453), 2 mg/day of ALA (n = 467), EPA–DHA plus ALA (n = 458), or placebo (n = 472). Serum testosterone levels were assessed at baseline and after 41 months using whole day blood samples obtained at the subjects’ home or at the hospital. Subjects were on average age of 68.4 (SD 5.3) years old and had baseline mean serum total testosterone of 14.8 (SD 5.6) nmol/L. The four randomized groups did not differ for baseline characteristics. ALA, EPA–DHA, and EPA–DHA plus ALA supplementation did not affect serum total testosterone compared to placebo. Moreover, n-3 fatty acid supplementation did not affect the risk of incident testosterone deficiency (n = 76 with total testosterone
Metabolic Effects of n-3 PUFA as Phospholipids Are Superior to Triglycerides in Mice Fed a High-Fat Diet: Possible Role of Endocannabinoids
Rossmeisl, M. ; Jilkova, Z.M. ; Kuda, O. ; Jelenik, T. ; Medrikova, D. ; Stankova, B. ; Kristinsson, B. ; Haraldsson, G.G. ; Svensen, H. ; Stoknes, I. ; Sjövall, P. ; Magnusson, Y. ; Balvers, M.G.J. ; Verhoeckx, K.C.M. ; Tvrzicka, E. ; Bryhn, M. ; Kopecky, J. - \ 2012
PLoS ONE 7 (2012)6. - ISSN 1932-6203
krill oil supplementation - tof-sims analysis - seal blubber oil - adipose-tissue - fish-oil - eicosapentaenoic acid - insulin sensitivity - induced obesity - cb1 antagonism - serum-lipids
Background n-3 polyunsaturated fatty acids, namely docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), reduce the risk of cardiovascular disease and can ameliorate many of obesity-associated disorders. We hypothesised that the latter effect will be more pronounced when DHA/EPA is supplemented as phospholipids rather than as triglycerides. Methodology/Principal Findings In a ‘prevention study’, C57BL/6J mice were fed for 9 weeks on either a corn oil-based high-fat obesogenic diet (cHF; lipids ~35% wt/wt), or cHF-based diets in which corn oil was partially replaced by DHA/EPA, admixed either as phospholipids or triglycerides from marine fish. The reversal of obesity was studied in mice subjected to the preceding cHF-feeding for 4 months. DHA/EPA administered as phospholipids prevented glucose intolerance and tended to reduce obesity better than triglycerides. Lipemia and hepatosteatosis were suppressed more in response to dietary phospholipids, in correlation with better bioavailability of DHA and EPA, and a higher DHA accumulation in the liver, white adipose tissue (WAT), and muscle phospholipids. In dietary obese mice, both DHA/EPA concentrates prevented a further weight gain, reduced plasma lipid levels to a similar extent, and tended to improve glucose tolerance. Importantly, only the phospholipid form reduced plasma insulin and adipocyte hypertrophy, while being more effective in reducing hepatic steatosis and low-grade inflammation of WAT. These beneficial effects were correlated with changes of endocannabinoid metabolome in WAT, where phospholipids reduced 2-arachidonoylglycerol, and were more effective in increasing anti-inflammatory lipids such as N-docosahexaenoylethanolamine. Conclusions/Significance Compared with triglycerides, dietary DHA/EPA administered as phospholipids are superior in preserving a healthy metabolic profile under obesogenic conditions, possibly reflecting better bioavalability and improved modulation of the endocannabinoid system activity in WAT
Preservation of Metabolic Flexibility in Skeletal Muscle by a Combined Use of n-3 PUFA and Rosiglitazone in Dietary Obese Mice
Horakova, O. ; Medrikova, D. ; Schothorst, E.M. van; Bunschoten, A. ; Keijer, J. - \ 2012
PLoS ONE 7 (2012)8. - ISSN 1932-6203
polyunsaturated fatty-acids - impaired glucose-tolerance - induced insulin-resistance - type-2 diabetes-mellitus - activated-receptor-alpha - fish-oil - weight-loss - marine origin - eicosapentaenoic acid - ceramidase activity
Insulin resistance, the key defect in type 2 diabetes (T2D), is associated with a low capacity to adapt fuel oxidation to fuel availability, i.e., metabolic inflexibility. This, in turn, contributes to a further damage of insulin signaling. Effectiveness of T2D treatment depends in large part on the improvement of insulin sensitivity and metabolic adaptability of the muscle, the main site of whole-body glucose utilization. We have shown previously in mice fed an obesogenic high-fat diet that a combined use of n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) and thiazolidinediones (TZDs), anti-diabetic drugs, preserved metabolic health and synergistically improved muscle insulin sensitivity. We investigated here whether n-3 LC-PUFA could elicit additive beneficial effects on metabolic flexibility when combined with a TZD drug rosiglitazone. Adult male C57BL/6N mice were fed an obesogenic corn oil-based high-fat diet (cHF) for 8 weeks, or randomly assigned to various interventions: cHF with n-3 LC-PUFA concentrate replacing 15% of dietary lipids (cHF+F), cHF with 10 mg rosiglitazone/kg diet (cHF+ROSI), cHF+F+ROSI, or chow-fed. Indirect calorimetry demonstrated superior preservation of metabolic flexibility to carbohydrates in response to the combined intervention. Metabolomic and gene expression analyses in the muscle suggested distinct and complementary effects of the interventions, with n-3 LC-PUFA supporting complete oxidation of fatty acids in mitochondria and the combination with n-3 LC-PUFA and rosiglitazone augmenting insulin sensitivity by the modulation of branched-chain amino acid metabolism. These beneficial metabolic effects were associated with the activation of the switch between glycolytic and oxidative muscle fibers, especially in the cHF+F+ROSI mice. Our results further support the idea that the combined use of n-3 LC-PUFA and TZDs could improve the efficacy of the therapy of obese and diabetic patients.
Effect of corn silage harvest maturity and concentrate type on milk fatty acid composition of dairy cows
Khan, N.A. ; Tewoldebrhan, T.A. ; Zom, R.L.G. ; Cone, J.W. ; Hendriks, W.H. - \ 2012
Journal of Dairy Science 95 (2012)3. - ISSN 0022-0302 - p. 1472 - 1483.
conjugated linoleic acids - trans octadecenoic acid - replacing grass-silage - maize silage - rumen fermentation - detergent fiber - sunflower oil - duodenal flow - linseed oil - fish-oil
The variation in maturity at harvest during grain filling has a major effect on the carbohydrate composition (starch:NDF ratio) and fatty acid (FA) content of corn silages, and can alter the FA composition of milk fat in dairy cows. This study evaluated the effect of silage corn (cv. Atrium) harvested and ensiled at targeted DM contents of 300, 340, 380, and 420g/kg of fresh weight and fed to dairy cows in combination with a highly degradable carbohydrate (HC) or low-degradable carbohydrate concentrate, on the nutrient intake, milk yield, and composition of milk and milk fat. Sixty-four multiparous Holstein-Friesian dairy cows in their first week of lactation were assigned to the 8 dietary treatments according to a randomized complete block design. The 8 dietary treatments consisted of a factorial combination of the 4 corn silages and the 2 concentrates. Corn silages were offered ad libitum as part of a basal forage mixture, whereas the concentrates were given at the rate of 8.5kg of DM/cow per day during the 15-wk experimental period. Dry matter, crude protein, and energy intakes did not differ across the corn silages. However, the intake of starch increased, and those of NDF and C18:3n-3 decreased with increasing maturation. Milk yield and composition were not different across the corn silages. Yield (kg/d) of milk, protein, and lactose was higher for low-degradable carbohydrate compared with HC concentrate-fed groups. Increasing maturity of corn silages decreased the content of C18:3n-3 and total n-3 and increased the n-6:n-3 ratio in milk fat. Concentrate type significantly altered the composition of all trans FA, except C18:2 trans-9,12. Inclusion of the HC concentrate in the diets increased the contents of all C18:1 trans isomers, C18:2 cis-9,trans-11, and C18:2 trans-10,cis-12 conjugated linoleic acid in milk fat. Milk fat composition was strongly influenced by the stage of lactation (wk 3 to 10). The content of all even short- and medium-chain FA changed with lactation, except C8:0 and C10:0. The content of C12:0, C14:0, and C16:0 and total saturated FA increased and the content of C18:0, C18:1 cis total, and total cis monounsaturated FA decreased with lactation. Maturity of the corn silages at harvest did not affect the production performance of dairy cows, but resulted in a decreased content of C18:3n-3, total n-3, and an increased n-6:n-3 ratio in the milk fat of dairy cows.
Effects of n-3 fatty acids on cognitive decline: A randomized double-blind, placebo-controlled trial in stable myocardial infarction patients
Geleijnse, J.M. ; Giltay, E.J. ; Kromhout, D. - \ 2012
Alzheimer's & Dementia 8 (2012)4. - ISSN 1552-5260 - p. 278 - 287.
alpha-linolenic acid - cardiovascular risk-factors - alzheimer-disease - dietary-intake - cardiac-arrest - dementia risk - fish-oil - health - omega-3-fatty-acids - supplementation
Background Epidemiological studies suggest a protective effect of n-3 fatty acids derived from fish (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) against cognitive decline. For a-linolenic acid (ALA) obtained from vegetable sources, the effect on cognitive decline is unknown. We examined the effect of n-3 fatty acid supplementation on cognitive decline in coronary heart disease patients. Methods The analysis included 2911 coronary patients (78% men) aged 60 to 80 years who participated in a double-blind placebo-controlled trial of n-3 fatty acids and cardiovascular diseases (Alpha Omega Trial). By using a 2 × 2 factorial design, patients were randomly assigned to margarines that provided 400 mg/d of EPA–DHA, 2 g/d of ALA, both EPA–DHA and ALA, or placebo for 40 months. Cognitive function was assessed by the Mini-Mental State Examination (MMSE) at baseline and after 40 months. The effect of n-3 fatty acids on change in MMSE score was assessed using analysis of variance. Logistic regression analysis was used to examine the effects on risk of cognitive decline, defined as a decrease of 3 or more points in MMSE score or incidence of dementia. Results Patients in the active treatment groups had an additional intake of 384 mg of EPA–DHA, 1.9 g of ALA, or both. The overall MMSE score in this cohort was 28.3 ± 1.6 points, which decreased by 0.67 ± 2.25 points during follow-up. Changes in MMSE score during intervention did not differ significantly between EPA–DHA and placebo (-0.65 vs -0.69 points, P = .44) or between ALA and placebo (-0.60 vs -0.74 points, P = .12). The risk of cognitive decline was 1.03 (95% confidence interval: 0.84–1.26, P = .80) for EPA–DHA (vs placebo) and 0.90 (0.74–1.10, P = .31) for ALA (vs placebo). Conclusion This large intervention study showed no effect of dietary doses of n-3 fatty acids on global cognitive decline in coronary heart disease patients. Keywords
Dietary supplementation with dimethylglycine affects broiler performance and plasma metabolites depending on dose and dietary fatty acid profile
Kalmar, I.D. ; Cools, A. ; Verstegen, M.W.A. ; Huyghebaert, G. ; Buyse, J. ; Roose, P. ; Janssens, G.P.J. - \ 2011
Journal of Animal Physiology and Animal Nutrition 95 (2011)2. - ISSN 0931-2439 - p. 146 - 153.
vitamin-e - fish-oil - resistance - hypertension
The effect of dietary supplementation with N,N-dimethylglycine sodium salt (Na-DMG) was evaluated in a feeding trial with 1500 1-day-old broiler chicks (Cobb 500). DMG was supplemented at 0, 0.1, 0.2, 0.5 or 1 g Na-DMG/kg feed to a ration with either animal fat (chicken fat) or vegetal fat (soy oil) as main fat source. In the vegetal fat diets, production value was significantly linearly improved by supplementation with DMG up to 11%. Irrespective of dietary fat source, abdominal fat percentage was significantly linearly reduced up to 24% and meat yield tended to increase linearly with DMG level up to 4%. In the vegetal fat groups, DMG significantly lowered abdominal fat pad by up to 38% and tended to increase meat yield up to 6% at the highest dose. Fasted non-esterified fatty acid level significantly decreased with increasing DMG level up to 36% and thiobarbituric acid reactive species (TBARS) decreased with a statistical trend up to 46% at the highest dose. In vegetal fat diets, addition of DMG resulted in significant lower TBARS level by 56% at the highest dose. Finally, a significant quadratic effect on ascites heart index was present in the vegetal fat diets, with a minimal value at 0.5 g Na-DMG/kg. In conclusion, dietary supplementation with DMG may improve technical and slaughter performance, and may reduce oxidative stress and pulmonary hypertension, but the degree of effects is modulated by fatty acid profile of the diet. Herewith, effects are more pronounced in a diet rich in polyunsaturated fatty acids compared with a diet rich in saturated and monounsaturated fatty acids.
Effects of forage type, forage to concentrate ratio, and crushed linseed supplementation on milk fatty acid profile in lactating dairy cows
Sterk, A.R. ; Johansson, B.E.O. ; Taweel, H.Z.H. ; Murphy, M. ; Vuuren, A.M. van; Hendriks, W.H. ; Dijkstra, J. - \ 2011
Journal of Dairy Science 94 (2011)12. - ISSN 0022-0302 - p. 6078 - 6091.
conjugated linoleic acids - sunflower oil - feed-intake - fish-oil - diet - biohydrogenation - rumen - silage - responses - trans-10
The effects of an increasing proportion of crushed linseed (CL) in combination with varying forage type (grass or corn silage) and forage to concentrate ratio (F:C), and their interactions on milk fatty acid (FA) profile of high-producing dairy cows was studied using a 3-factor Box-Behnken design. Sixteen Holstein and 20 Swedish Red cows were blocked according to breed, parity, and milk yield, and randomly assigned to 4 groups. Groups were fed different treatment diets formulated from combinations of the 3 main factors each containing 3 levels. Forage type (fraction of total forage dry matter, DM) included 20, 50, and 80% grass silage, with the remainder being corn silage. The F:C (DM basis) were 35:65, 50:50, and 65:35, and CL was supplied at 1, 3, and 5% of diet DM. Starch and neutral detergent fiber content (DM basis) of the treatment diets ranged from 117 to 209 g/kg and 311 to 388 g/kg, respectively. Thirteen treatment diets were formulated according to the Box-Behnken design. During 4 experimental periods of 21 d each, all treatment diets were fed, including a repetition of the center point treatment (50% grass silage, 50:50 F:C, 3% CL) during every period. Intake, production performance, and milk FA profile were measured, and response surface equations were derived for these variables. Shifting from 80% grass silage to 80% corn silage in the diet linearly increased dry matter intake (DMI), net energy for lactation (NEL) intake, cis-9,cis-12-C18:2 (C18:2n-6) intake, and milk yield, and linearly decreased cis-9,cis-12,cis-15-C18:3 (C18:3n-3) intake and milk fat content. Shifting from a high forage to a high concentrate diet linearly increased DMI, NEL intake, C18:2n-6 intake, and milk yield, and decreased milk fat content. Supplementation of CL linearly increased C18:3n-3 intake, but had no effect on DMI, NEL intake, milk yield, or milk fat content. Shifting from 80% grass silage to 80% corn silage linearly increased proportions of trans-10-C18:1 and C18:2n-6 in milk fat, whereas the proportions of trans-11,cis-15-C18:2 and C18:3n-3 linearly decreased. Significant interactions between CL supplementation and F:C were found for proportions of trans-10-C18:1, trans-15-C18:1, cis-15-C18:1, trans-11,cis-15-C18:2, and C18:3n-3 in milk fat, with the highest levels achieved when the diet contained 5% CL and a 35:65 F:C ratio. The effect of supplementing CL on several milk FA proportions, including C18:2n-6 and C18:3n-3, depends significantly on the F:C ratio and forage type in the basal diet.
Dose-dependent effects of leucine supplementation on preservation of muscle mass in cancer cachectic mice
Peters, S.J. ; Helvoort, A. van; Kegler, D. ; Argiles, J.M. ; Luiking, Y.C. ; Laviano, A. ; Bergenhenegouwen, J. van; Deutz, N.E.P. ; Haagsman, H.P. ; Gorselink, M. ; Norren, K. van - \ 2011
Oncology Reports : an international journal devoted to fundamental and applied research in oncology 26 (2011)1. - ISSN 1021-335X - p. 247 - 254.
chain amino-acids - urinary 3-methylhistidine excretion - tumor-bearing rats - skeletal-muscle - protein-synthesis - pancreatic-cancer - weight-loss - fish-oil - in-vivo - colon-26 adenocarcinoma
Cancer cachexia, which is characterized by muscle wasting, is associated with increased morbidity and mortality. Because muscle protein synthesis may be increased and protein breakdown reduced by leucine supplementation, we used the C26 tumor-bearing cachectic mouse model to assess the effects of dietary supplementation with leucine on muscle weight and the markers of muscle protein breakdown (mRNA of atrogin and murf). Male CD2F1 mice were subcutaneously inoculated with tumor cells (tumor-bearing mice; TB) or were sham injected (control; C). They were fed standard diets or diets supplemented with leucine [1 gr (TB1Leu) or 8 gr (TB8Leu) supplemented leucine per kg feed]; TB and C received 8.7% Leu/g protein, TB1Leu received 9.6% Leu/g protein and TB8Leu received 14.6 Leu/g protein. After 21 days, the following were determined: body weights, plasma amino-acid concentrations, tumor size and muscle mass of the gastrocnemius (mG), tibialis anterior (mTA), extensor digitorum longus (mEDL) and soleus (mS) muscles. In tumor-bearing (TB) mice, carcass and skeletal muscle masses decreased, and levels of atrogin and murf mRNA in the mEDL increased. Muscle-mass loss was counteracted dose-dependently by leucine supplementation: relative to TB, the mass of the mG was +23% in TB8Leu, and +22% in mTA (p
Effects of feeding rapeseed oil, soybean oil, or linseed oil on stearoyl-CoA desaturase expression in the mammary gland of dairy cows
Jacobs, A.A.A. ; Baal, J. van; Smits, M.A. ; Taweel, H.Z.H. ; Hendriks, W.H. ; Vuuren, A.M. van; Dijkstra, J. - \ 2011
Journal of Dairy Science 94 (2011)2. - ISSN 0022-0302 - p. 874 - 887.
conjugated linoleic-acid - milk-fat synthesis - fish-oil - lipid-metabolism - messenger-rna - sunflower oil - intestinal digestibility - nutritional regulation - seasonal-variation - lipogenic genes
Stearoyl-CoA desaturase (SCD) is an important enzyme in the bovine mammary gland, and it introduces a double bond at the ¿(9) location of primarily myristoyl-, palmitoyl-, and stearoyl-CoA. The main objective of this study was to compare the effects of various fatty acids (FA) typically present in dairy cow rations on the expression of SCD1 and SCD5 in the mammary gland of dairy cows. Twenty-eight Holstein-Friesian cows were randomly assigned to 1 of 4 dietary treatments. The dietary treatments were a basal diet supplemented (dry matter basis) with 2.7% rapeseed oil as a source of C18:1 cis-9; 2.7% soybean oil as a source of C18:2 cis-9,12; 2.7% linseed oil as a source of C18:3 cis-9,12,15; or 2.7% of a 1:1:1 mixture of the 3 oils. The oil supplements were included in the concentrate, which was fed together with corn silage and grass silage. In addition, cows were grazing on pasture, consisting mainly of perennial ryegrass, during the day. Biopsies from the mammary gland were taken and analyzed for mRNA expression of SCD1 and SCD5 by using quantitative real-time PCR. Milk yield as well as milk protein and fat contents did not differ among the 4 dietary treatments. Dietary supplementation with rapeseed oil and linseed oil increased proportions of C18:1 cis-9 and C18:3 cis-9,12,15 in blood plasma, respectively, compared with the other treatments. Supplementation with soybean oil and linseed oil increased milk FA proportions of C18:2 cis-9,12 and C18:3 cis-9,12,15, respectively, but supplementation with rapeseed oil did not increase C18:1 cis-9 in milk. Mammary SCD1 expression was reduced by supplementation of soybean oil compared with rapeseed oil and linseed oil. In contrast, SCD5 expression did not differ among the 4 treatments. The C16 and C18 desaturation indices, representing proxies for SCD activity, were lower for the soybean oil diet compared with the diet supplemented with a mixture of the 3 oils. In conclusion, our study shows that mammary SCD1 expression is significantly downregulated in dairy cows by feeding unprotected soybean oil compared with rapeseed oil or linseed oil, and this is partially reflected by the lower desaturase indices in the milk. Furthermore, mammary SCD5 expression appears to be differently regulated than expression of SCD1
Enrichment of the African catfish Clarias gariepinus (Burchell) with functional selenium originating from garlic: effect of enrichment period and depuration on total selenium level and sensory properties
Schram, E. ; Schelvis-Smit, A.A.M. ; Heul, J.W. van der; Luten, J.B. - \ 2010
Aquaculture Research 41 (2010)6. - ISSN 1355-557X - p. 793 - 803.
fatty-acid-composition - oil finishing diet - cancer prevention - fish-oil - speciation
We wanted to optimize the procedure for the selenium enrichment of farmed African catfish, using garlic as dietary selenium source. In the first experiment we established the relation between the length of the selenium enrichment period and the resulting total selenium level in the fillet of the fish. It was found that at a dietary level of 11.7 mg kg-1 Se, a total selenium level in the fillet of 0.7 mg kg-1 was reached in a relatively short enrichment period of 10 days before harvest. In the second experiment we studied the effect of depuration on the selenium level in the fillet and the sensory properties of selenium-enriched African catfish. It was found that total selenium levels in the fillet were not affected during a 7-day depuration period, while garlic odours and flavours in the raw and cooked fillets were significantly reduced after 2 days of depuration. We concluded that selenium enrichment of farmed African catfish can be obtained by selenium-enriched finishing diets, while garlic odours and flavours resulting from dietary garlic can be effectively reduced in the fillet during a short depuration period without negatively affecting fillet levels of total selenium.
Alpha-Linolenic Acid: Is It Essential to Cardiovascular Health?
Geleijnse, J.M. ; Goede, J. de; Brouwer, I.A. - \ 2010
Current Atherosclerosis Reports 12 (2010)6. - ISSN 1523-3804 - p. 359 - 367.
coronary-heart-disease - n-3 fatty-acid - myocardial-infarction - fish-oil - secondary-prevention - national heart - reduced risk - flaxseed oil - double-blind - trial
There is a large body of scientific evidence that has been confirmed in randomized controlled trials indicating a cardioprotective effect for omega-3 fatty acids from fish. For alpha-linolenic acid (ALA), which is the omega-3 fatty acid from plants, the relation to cardiovascular health is less clear. We reviewed the recent literature on dietary ALA intake, ALA tissue concentrations, and cardiovascular health in humans. Short-term trials (6–12 weeks) in generally healthy participants mostly showed no or inconsistent effects of ALA intake (1.2–3.6 g/d) on blood lipids, low-density lipoprotein oxidation, lipoprotein(a), and apolipoproteins A-I and B. Studies of ALA in relation to inflammatory markers and glucose metabolism yielded conflicting results. With regard to clinical cardiovascular outcomes, there is observational evidence for a protective effect against nonfatal myocardial infarction. However, no protective associations were observed between ALA status and risk of heart failure, atrial fibrillation, and sudden death. Findings from long-term trials of ALA supplementation are awaited to answer the question whether food-based or higher doses of ALA could be important for cardiovascular health in cardiac patients and the general population
The reliability of three depression rating scales in a general population of Dutch older persons
Rest, O. van de; Zwaluw, N.L. van der; Beekman, A.T.F. ; Groot, C.P.G.M. de; Geleijnse, J.M. - \ 2010
International Journal of Geriatric Psychiatry 25 (2010)10. - ISSN 0885-6230 - p. 998 - 1005.
nursing-home patients - ces-d - coefficient alpha - controlled-trial - fish-oil - validity - 15-item - validation - versions - performance
Objective To compare the reliability of three rating scales for assessing depressive symptoms in a community-based, non-clinically depressed older population. Methods The study sample comprised of 302 independently living subjects aged 65 years or older. Depressive symptoms were assessed using the centre for epidemiologic studies depression scale (CES-D), the geriatric depression scale (GDS-15) and the Montgomery and Åsberg depression rating scale (MADRS) at three time points: at baseline, after 13 weeks (except the GDS-15) and after 26 weeks. Three dimensions of reliability were compared: (i) internal consistency (Cronbach's alpha), (ii) reproducibility (Spearman correlations) and (iii) the intra- and inter-rater reliability (Spearman correlations to compare the differences between correlations of subjects tested by the same vs. different raters at three time points). Results Cronbach's alpha was high for the CES-D (0.84), good for the MADRS (0.72) and relatively low for the GDS-15 (0.55). Reproducibility was also higher for the CES-D (0.71) than for the MADRS (0.61) and the GDS-15 (0.52). The rater had little influence on CES-D scores (intra/inter-rater ratio = 0.99). The GDS-15 and the MADRS, however, performed better when administered by the same rater. Conclusions The CES-D was the most reliable scale for measuring depressive symptoms in a non-clinically depressed older population
Short communication: Genome-wide scan for bovine milk-fat composition. II. Quantitative trait loci for long-chain fatty acids
Schennink, A. ; Stoop, W.M. ; Visker, M.H.P.W. ; Poel, J.J. van der; Bovenhuis, H. ; Arendonk, J.A.M. van - \ 2009
Journal of Dairy Science 92 (2009)9. - ISSN 0022-0302 - p. 4676 - 4682.
dairy-cattle - genetic-parameters - f-2 population - rat-liver - fish-oil - dgat1 - polymorphism - trans - cows - qtl
We present the results of a genome-wide scan to identify quantitative trait loci (QTL) that contribute to genetic variation in long-chain milk fatty acids. Milk-fat composition phenotypes were available on 1,905 Dutch Holstein-Friesian cows. A total of 849 cows and their 7 sires were genotyped for 1,341 single nucleotide polymorphisms across all Bos taurus autosomes (BTA). We detected significant QTL on BTA14, BTA15, and BTA16: for C18:1 cis-9, C18:1 cis-12, C18:2 cis-9,12, CLA cis-9,trans-11, C18:3 cis-9,12,15, the C18 index, the total index, total saturated fatty acids, total unsaturated fatty acids (UFA), and the ratio of saturated fatty acids:unsaturated fatty acids on BTA14; for C18:1 trans fatty acids on BTA15; and for the C18 and CLA indices on BTA16. The QTL explained 3 to 19% of the phenotypic variance. Suggestive QTL were found on 16 other chromosomes. The diacylglycerol acyltransferase 1 (DGAT1) K232A polymorphism on BTA14, which is known to influence fatty acid composition, most likely explains the QTL that was detected on BTA14