Effects of fatty acid metabolites on nocturia.

Dysregulation of circadian rhythm can cause nocturia. Levels of fatty acid metabolites, such as palmitoylethanolamide (PEA), 9-hydroxy-10E,12Z-octadecadienoic acid (9-HODE), and 4-hydroxy-5E,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid (4-HDoHE), are higher in the serum of patients with nocturia; however, the reason remains unknown. Here, we investigated the circadian rhythm of fatty acid metabolites and their effect on voiding in mice. WT and Clock mutant (ClockΔ19/Δ19) mice, a model for nocturia with circadian rhythm disorder, were used. Levels of serum PEA, 9-HODE, and 4-HDoHEl were measured every 8 h using LC/MS. Voiding pattern was recorded using metabolic cages after administration of PEA, 9-HODE, and 4-HDoHE to WT mice. Levels of serum PEA and 9-HODE fluctuated with circadian rhythm in WT mice, which were lower during the light phase. In contrast, circadian PEA and 9-HODE level deteriorated or retreated in ClockΔ19/Δ19 mice. Levels of serum PEA, 9-HODE, and 4-HDoHE were higher in ClockΔ19/Δ19 than in WT mice. Voiding frequency increased in PEA- and 4-HDoHE-administered mice. Bladder capacity decreased in PEA-administered mice. The changes of these bladder functions in mice were similar to those in elderly humans with nocturia. These findings highlighted the novel effect of lipids on the pathology of nocturia. These may be used for development of biomarkers and better therapies for nocturia.

The Sum of Plasma Fatty Acids iso16:0, iso17:0, trans11-18:1, cis9, trans11-CLA, and cis6-18:1 as Biomarker of Dairy Intake Established in an Intervention Study and Validated in the EPIC Cohort of Gipuzkoa.

The questioned reliability of 15:0, 17:0, and trans9-16:1 acids as biomarkers of dairy fat intake also questions the relationship between the intake of these products and their health effects. Two studies were conducted in the same geographical region. In an intervention study, volunteers followed a diet rich in dairy products followed by a diet without dairy products. Plasma and erythrocyte fatty acids (FA) were analyzed, and their correlations with dairy product intakes were tested. The FA biomarkers selected were validated in the Gipuzkoa cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC) observational study. The correlation coefficients between plasma concentrations of iso16:0, iso17:0, trans11-18:1, cis9, trans11-18:2, and cis6-18:1 and the dairy fat ingested are similar in both studies, indicating that their concentration increases by 0.8 µmol/L per gram of dairy fat ingested. The biomarkers are positively related to plasma triglycerides (r = 0.324 and 0.204 in the intervention and observational studies, respectively) and total cholesterol (r = 0.459 and 0.382), but no correlation was found between the biomarkers and atherogenicity indexes. In conclusion, the sum of the plasma concentration of the selected FAs can be used as biomarkers of dairy product consumption. A linear relationship exists between their plasma concentrations and ruminant product intake. These biomarkers allow for obtaining consistent relationships between dairy intake and plasma biochemical parameters.

The relationship between plasma ß-hydroxybutyric acid and conjugated linoleic acid in milk as a biomarker for early diagnosis of ketosis in postpartum Polish Holstein-Friesian cows.

BACKGROUND: The aim of this study was to investigate the association between plasma ß-hydroxybutyric acid (BHBA) and conjugated linoleic acid in postpartum Polish Holstein-Friesian (PHF) cows. The experiment was carried out at an experimental dairy farm, where a herd of approximately 350 cows was kept. Samples were taken at six time points: between days 5-7, 8-14, 15-21, 22-28, 29-35, and 36-42, resulting in 510 samples of both milk and blood. The cows involved in the experiment were divided into two groups - ketotic and healthy - by taking into account general health symptoms, blood serum BHBA, and non-esterified fatty acids (NEFA) concentration at 5-7 days postpartum. RESULTS: In the first week of lactation, at 5-7 day in milk (DIM), the study showed a 53% lower level of C18:2 cis-9 trans-11 (CLA9) and an 80% lower level of C18:2 trans-10 cis-12 (CLA10) in cows with diagnosed ketosis compared to healthy cows. In the second week of lactation (8-14 DIM), a 34% lower level of CLA9 and a 54% lower level of CLA10 was found in the group of cows with BHBA levels > 1.2 mmol/L. Additionally, Pearson correlation analysis showed significant negative correlation between BHBA x CLA9 and BHBA x CLA10 in the first week of lactation: - 0.732and - 0.821, respectively. CONCLUSION: The study shows that that both CLA9 and CLA10 can be used as markers for the early diagnosis of elevated blood levels of BHBA in postpartum Polish Holstein-Friesian cows.

Diabetes Mellitus, Nonalcoholic Fatty Liver Disease, and Conjugated Linoleic Acid (Omega 6): What Is the Link?

BACKGROUND AND OBJECTIVE: Type 2 DM and obesity are the coming epidemics and their association with NAFLD is well established; essential fatty acids are vital for body health yet the body cannot make them; 2 essential fatty acids are especially important: linoleic (omega-6) and alpha-linoleic (omega-3) acids; they can be considered as "bioactive lipids" and serve as functional foods. METHODS: 50 type 2 Egyptian diabetic patients controlled on oral hypoglycemic drugs together with 20 age- and sex-matched healthy participants were enrolled in the study; all were subjected to complete history taking, BMI, fasting plasma glucose, HOMA-IR, ALT, AST, GGT, urea and creatinine, total lipid profile, hepatitis markers including hepatitis B surface antigen and hepatitis C virus antibodies, conjugated linoleic fatty acid "CLA," and abdominal ultrasound for grading of NAFLD. RESULTS: Our study in Egyptian diabetics with NAFLD revealed a low level of serum CLA compared to healthy control; such deficiency was more marked with advanced grades of NAFLD; lowest levels were observed in those with severe steatosis (NASH) with definite association between CLA and obesity. CONCLUSION: Insulin resistance is the main link between NAFLD, diabetes, and obesity. Conjugated linoleic acid (CLA) has a role in fat deposition in the liver and in development and improvement of insulin resistance. Fatty food had a documented role in the pathogenesis of obesity and diabetes but it can also be the cure.

Circulating fatty acids as biomarkers of dairy fat intake: data from the lifelines biobank and cohort study.

Background: C14:0, C15:0, C17:0 and trans-C16:1(n-7) are often used as biomarkers for dairy fat intake. Trans-C18:1(n-7) and CLA, two fatty acids which are also present in dairy, have hardly been explored. We investigated whether trans-C18:1(n-7) and CLA can enrich the existing biomarker portfolio. Methods: Data were obtained from Lifelines (n = 769). Dairy fat intake was determined by FFQ. Fatty acids were measured in fasting plasma triglycerides (TG), phospholipids (PL) and cholesterol esters (CE). Results: Median (25th-75th percentile) intakes of dairy and dairy fat were 322(209-447) and 12.3(8.4-17.4) g/d respectively. A pilot study showed that trans-C18:1(n-7) and CLA were only detectable in TG and PL. Of the established markers, TG C15:0 was most strongly associated with dairy fat intake (standardized ß (std.ß) = 0.286, R2 = 0.111). Of the less established markers, TG trans-C18:1(n-7) was most strongly associated with dairy fat intake (Std.ß = 0.292, R2 = 0.115), followed by PL CLA (Std.ß = 0.272, R2 = 0.103) and PL trans-C18:1(n-7) (Std.ß = 0.269, R2 = 0.099). In TG, a combination of C15:0 and trans-C18:1(n-7) performed best (R2 = 0.128). In PL, a combination of C14:0, C15:0, trans-C18:1(n-7) and CLA performed best (R2 = 0.143). Conclusion: Trans-C18:1(n-7) and CLA can be used as biomarkers of dairy fat intake. Additionally, combining established with less established markers allowed even stronger predictions for dairy fat intake.

Evaluation of conjugated linoleic acid supplementation on markers of joint inflammation and cartilage metabolism in young horses challenged with lipopolysaccharide.

Seventeen yearling Quarter Horses were used in a randomized complete block design for a 56-d trial to determine ability of dietary CLA to mitigate joint inflammation and alter cartilage turnover following an inflammatory insult. Horses were blocked by age, sex, and BW, and randomly assigned to dietary treatments consisting of commercial concentrate offered at 1% BW (as-fed) supplemented with either 1% soybean oil (CON; n = 6), 0.5% soybean oil and 0.5% CLA (LOW; n = 5; 55% purity; Lutalin, BASF Corp., Florham Park, NJ), or 1% CLA (HIGH; n = 6) top-dressed daily. Horses were fed individually every 12 h and offered 1% BW (as-fed) coastal bermudagrass (Cynodon dactylon) hay daily. This study was performed in 2 phases: phase I (d 0 to d 41) determined incorporation of CLA into plasma and synovial fluid; phase II (d 42 to d 56) evaluated potential of CLA to mitigate intra-articular inflammation and alter cartilage metabolism. Blood and synovial fluid were collected at 7- and 14-d intervals, respectively, to determine fatty acid concentrations. On d 42, carpal joints within each horse were randomly assigned to receive intra-articular injections of 0.5 ng lipopolysaccharide (LPS) derived from Escherichia coli 055:B5 or sterile lactated Ringer's solution. Synovial fluid samples were obtained at preinjection h 0 and 6, 12, 24, 168, and 336 h postinjection, and analyzed for prostaglandin E2 (PGE2), carboxypeptide of type II collagen (CPII), and collagenase cleavage neopeptide (C2C). Data were analyzed using PROC MIXED procedure of SAS. Horses receiving the CON diet had undetectable levels of CLA for the duration of the study. A quadratic dose response was observed in concentrations of CLA in plasma and synovial fluid (P < 0.01). A negative quadratic dose response was observed for plasma arachidonic acid (20:4) with a reduction in concentration to d 14 in HIGH horses (P = 0.04). Synovial fluid 20:4 tended to decrease in horses receiving the HIGH diet (P = 0.06). Post LPS injection, synovial PGE2 was not affected by dietary treatment (P = 0.15). Synovial C2C was lower in HIGH horses (P = 0.05), and synovial CPII tended to be greater in LOW horses than HIGH and CON horses (P = 0.10). In conclusion, dietary CLA incorporated into plasma and synovial fluid prior to LPS challenge. Dietary CLA did not influence inflammation; however, there was a reduction in cartilage degradation and an increase in cartilage regeneration.

Serum Conjugated Linoleic Acid and Risk of Incident Heart Failure in Older Men: The British Regional Heart Study.

BACKGROUND: Evidence largely from animal studies suggests that conjugated linoleic acid (CLA) may have cardiovascular health benefits. However, few prospective studies have examined the association between CLA and cardiovascular disease. We have prospectively examined the association between serum CLA and incident coronary heart disease and heart failure (HF) in older men. METHODS AND RESULTS: Prospective study of 3806 men, aged 60 to 79 years, without prevalent HF followed up for an average of 13 years, during which there were 295 incident HF cases. A high-throughput serum nuclear magnetic resonance metabolomics platform was used to measure CLA concentration in serum, expressed as a percentage of total fatty acids (CLA%). CLA% was adversely associated with cholesterol and high-density lipoprotein cholesterol but was inversely associated with C-reactive protein and NT-proBNP (N-terminal pro-B-type natriuretic peptide; a marker of ventricular stress). No association was seen between CLA% and incident coronary heart disease. High CLA% was associated with significantly reduced risk of HF after adjustment for HF risk factors and C-reactive protein (hazard ratio [95% confidence interval], 0.64 [0.43-0.96]; quartile 4 versus quartile 1). Elevated CLA% was associated with reduced HF risk only in those with higher dairy fat intake, a major dietary source of CLA (test for interaction P=0.03). The reduced risk of HF was partially explained by NT-proBNP. High dairy fat intake was not associated with incident coronary heart disease but was associated with reduced risk of HF, largely because of the inverse effect of CLA. CONCLUSIONS: The finding that high CLA% is associated with lower risk of incident HF in older men requires confirmation in larger studies.

Impact of conjugated linoleic acid administered to rats prior and after carcinogenic agent on arachidonic and linoleic acid metabolites in serum and tumors.

The objective of the study was to assess the influence of conjugated linoleic acid (CLA) daily supplementation prior and after carcinogenic agent on the concentrations of eicosanoids - metabolites of arachidonic acid (15-, 12- or 5-hydroxyeicosatetraenoic acids (15-, 12-, 5-HETE), prostaglandin E2 (PGE2)) and linoleic acid (13- or 9-hydroxyoctadecadienoic acids (13-, 9-HODE)) in rat serum and 7,12-dimethylbenz[a]anthracene (DMBA)-induced tumors. Female rats were randomised into six groups, receiving 1% or 2% Bio-C.L.A or plant oil since the 37th day of life throughout the whole experiment. Some rats (50-day-old) were administered DMBA to induce tumors. Eicosanoids were analyzed with LC-MS/MS. The study indicated that CLA supplemented daily to rats prior and after carcinogen administration affected concentrations of arachidonic and linoleic acid metabolites in rat serum and induced tumors. However, ratios of eicosanoids exerting opposite activities (e.g. 12-HETE/15-HETE) appear to act as more precise factors reflecting pathological changes in an organism than individual compounds.

Absorption Kinetics of the Main Conjugated Linoleic Acid Isomers in Commercial-Rich Oil after Oral Administration in Rats.

This study aimed to assess the oral absorption and plasma kinetics of two main isomers contained in commercial conjugated linoleic acid (CLA)-rich oil (Tonalin TG-80), rumenic acid (RA), and C18:2 trans-10, cis-12. The isomer plasma disposition after the single oral dose of 3000 mg of Tonalin TG-80/kg, containing 1200 mg/kg of each isomer, was studied in rats. The isomer plasma concentrations were determined by gas chromatography with flame ionization detection. The plasma kinetics showed rapid oral absorption of RA and C18:2 trans-10, cis-12 (t1/2a 0.34 ± 0.09 and 0.53 ± 0.01 h) and slow elimination (t1/2ß 25.68 ± 3.29 and 18.12 ± 1.71 h); the maximal isomer plasma concentrations (Cmax) of 8.48 ± 0.98 and 7.67 ± 0.80 µg mL-1, respectively, were estimated at 2.08 ± 0.14 and 2.26 ± 0.11 h. Our results from a preclinical kinetic study in rats help to design future studies in humans for evaluating the CLA isomer dose-response.

Organic food consumption during pregnancy and its association with health-related characteristics: the KOALA Birth Cohort Study.

OBJECTIVE: To investigate the associations of organic food consumption with maternal pre-pregnancy BMI, hypertension and diabetes in pregnancy, and several blood biomarkers of pregnant women. DESIGN: Prospective cohort study. SETTING: Pregnant women were recruited at midwives' practices and through channels related to consumption of food from organic origin. SUBJECTS: Pregnant women who filled in FFQ and donated a blood sample (n 1339). Participant groups were defined based on the share of consumed organic products; to discriminate between effects of food origin and food patterns, healthy diet indicators were considered in some statistical models. RESULTS: Consumption of organic food was associated with a more favourable pre-pregnancy BMI and lower prevalence of gestational diabetes. Compared with participants consuming no organic food (reference group), a marker of dairy products intake (pentadecanoic acid) and trans-fatty acids from natural origin (vaccenic and rumenic acids) were higher among participants consuming organic food (organic groups), whereas elaidic acid, a marker of the intake of trans-fatty acids found in industrially hydrogenated fats, was lower. Plasma levels of homocysteine and 25-hydroxyvitamin D were lower in the organic groups than in the reference group. Differences in pentadecanoic acid, vaccenic acid and vitamin D retained statistical significance when correcting for indicators of the healthy diet pattern associated with the consumption of organic food. CONCLUSIONS: Consumption of organic food during pregnancy is associated with several health-related characteristics and blood biomarkers. Part of the observed associations is explained by food patterns accompanying the consumption of organic food.

The effect of conjugated linoleic acid, acetate, and their interaction on adipose tissue lipid metabolism in nonlactating cows.

During biohydrogenation-induced milk fat depression, adipose tissue lipogenesis may be increased through nutrients spared from milk fat synthesis. However, the direct effect of trans-10,cis-12 conjugated linoleic acid (CLA) and the indirect effect of spared nutrients on adipose tissue lipogenesis during milk fat depression is not clear. The objective of this study was to determine the direct effect of CLA, spared acetate, and their interaction on adipose tissue lipogenesis using nonlactating dairy cows as an experimental model, which allows separation of the effect of CLA and nutrient sparing. Eight ruminally cannulated, multiparous nonlactating and pregnant Holstein cows were randomly assigned to treatments in a 4 × 4 Latin square design with a 2 × 2 factorial arrangement of treatments. Factors were CLA and acetate, and treatments were control (CON), rumen acetate infusions (Ac; continuous infusion of 7 mol/d adjusted to pH 6.1 with sodium hydroxide), abomasal infusion of trans-10,cis-12 CLA (CLA; 10 g/d of both trans-10,cis-12 CLA and cis-9,trans-11 CLA), and Ac + CLA (Ac + CLA). Dry matter intake was not affected by Ac, but tended to decrease by CLA. Plasma trans-10,cis-12 CLA concentration as a percentage of fatty acids was increased by 0.3 percentage points by CLA. No treatment effect was observed on plasma glucose and ß-hydroxybutyrate, but an interaction was observed of CLA and Ac on plasma insulin and nonesterified fatty acids. Insulin was increased 24% by CLA, but not by Ac + CLA, and nonesterified fatty acids were increased 55% by Ac + CLA, but not by CLA alone. Lipogenesis and oxidation capacity of adipose tissue explants were not affected by treatments. Adipose expression of key lipogenic factors (peroxisome proliferator-activated receptor γ2 and sterol response element binding protein 1c) were reduced by CLA, by the interaction of Ac and CLA (sterol response element binding protein 1c), and tended to be reduced with Ac (S14 and peroxisome proliferator-activated receptor γ1). Expression of several adipose lipogenic enzymes (fatty acid synthase, acetyl-CoA carboxylase, and stearoyl-CoA desaturase 1) was reduced by CLA and Ac. An interaction was observed of Ac and CLA for fatty acid binding protein 4, which was decreased by Ac, but not Ac + CLA. In conclusion, in the nonlactating cow, adipose tissue is sensitive to the anti-lipogenic effects of trans-10,cis-12 CLA at the transcription level and acetate does not stimulate lipogenesis.

Ruminant trans-fatty acids and risk of breast cancer: a systematic review and meta-analysis of observational studies.

INTRODUCTION: Ruminant trans-fatty acids, especially cis9, trans11-conjugated linoleic acid (c9,t11-CLA) and trans11-18:1 vaccenic acid (t11-18:1 VA) appear to have anticarcinogenic activity against breast cancer in animal and in vitro experiments. However, the results remain inconsistent. We therefore conducted a systematic review and meta-analysis to assess the association of c9,t11-CLA, and t11-18:1 VA (intake or serum levels) with breast cancer risk. EVIDENCE ACQUISITION: Relevant studies were identified by a search of PubMed, OVID, SCOPUS and Google scholar databases through 25 May 2015. We included case-control and cohort studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the association between c9,t11-CLA and t11-18:1 VA intake or their serum levels and the risk of breast cancer. This meta-analysis was conducted according to the guidelines for the meta-analysis of observational studies in epidemiology. EVIDENCE SYNTHESIS: Three studies on c9,t11-CLA and t11-18:1 VA serum levels and t11-18:1 VA intake were evaluated in the systematic review only (narrative synthesis) and four studies (2 case-control and 2 cohort studies on c9,t11-CLA intake) were included in the meta-analysis (quantitative synthesis). The pooled RR for the highest vs lowest category of c9,t11-CLA intake was 0.94 (95% CI: 0.64-1.25) with evidence of heterogeneity (with 67,533 participants, I2=78.3%, P=0.003). Studies that could not be included in the quantitative syntheses were inconclusive. CONCLUSIONS: No association was found between c9,t11-CLA intake and breast cancer risk, but the number of studies identified was small.

Preparation of Conjugated Linoleic Acid Microemulsions and their Biodistribution.

Conjugated linoleic acid (CLA) has several beneficial biological properties. Specifically, trans10, cis12-CLA, one of the CLA isomers, has strong physiologic activity against cancer and obesity. However, compared with cis9, trans11-CLA, a naturally occurring CLA isomer, trans10, cis12-CLA tends to be easily metabolized. Therefore, to make efficient use of its biological properties, it is necessary to overcome the rapid clearance of trans10, cis12-CLA from the blood. Here, we employed premix membrane emulsification to prepare two oil-in-water CLA microemulsions (CLA-ME), 100 nm CLA-ME and 200 nm CLA-ME, and investigated their pharmacokinetics in a mouse model. We report that 100 nm CLA-ME contributed to the concentration of blood CLA for longer than 200 nm CLA-ME, indicating that small CLA microparticles were more suitable for maintaining blood trans10, cis12-CLA levels in vivo. However, both CLA-ME could be hardly detected in blood and other tissues 24 h after administration, suggesting that additional strategies for prolonging CLA-ME half-life are required.

Dietary linseed oil with or without malate increases conjugated linoleic acid and oleic acid in milk fat and and gene expression in mammary gland and milk somatic cells of lactating goats.

Supplementary dietary plant oils have the potential to alter milk fatty acid composition in ruminants as a result of changes in the amount and kind of fatty acid precursors. We hypothesized that linseed oil in combination with malate (a key propionate precursor in the rumen) would increase ∆9 unsaturated fatty acids and specific gene expression in somatic cells and mammary glands of lactating goats. Twelve lactating goats were used in a 3 × 3 Latin square design. Treatments included the basal diet (CON), the CON plus 4% linseed oil (LO), and the CON plus 4% linseed oil and 2% -malate (LOM). Relative to CON, the LO and LOM supplements increased the daily intake of palmitic (16:0), stearic (18:0), oleic (18:1-9), linoleic (18:2-6), α-linolenic (18:3-3), and γ-linolenic acids (18:2-6); α-linolenic acid intake was increased over 9-fold, from 6.77 to over 51 g/d ( < 0.02). The LO and LOM supplements increased daily milk yield, milk fat yield, and milk fat percentage ( < 0.05). The LOM supplement also increased milk lactose percentage and daily yield ( = 0.03). Both the LO and LOM supplements increased plasma glucose and total cholesterol and decreased plasma ß-hydroxbutyrate concentrations ( = 0.03). The LO and LOM supplements increased concentrations of stearic acid; -vaccenic acid (TVA; 18:1-11); -9, -11 CLA; -10 -12 CLA; and α-linolenic acid in rumen fluid and increased the concentrations of oleic acid; TVA; -9, -11 CLA; -10, -12 CLA; and α-linolenic acid in plasma lipids and milk fat ( < 0.05). Conversely, the LO and LOM supplements decreased short- and medium-chain SFA, including lauric (12:0), myristic (14:0), and palmitic acids, in plasma and milk fat ( < 0.05). Relative mRNA levels for and () gene expression were increased in somatic cells and mammary gland tissue by LO and LOM ( < 0.05). We conclude that the higher intake and ruminal production of stearic acid promoted SCD gene expression in somatic cells and mammary tissue. Furthermore, milk somatic cells are a suitable substitute for documenting treatment effects of dietary oils on gene expression in goat mammary tissue.

Medium-chain triglycerides and conjugated linoleic acids in beverage form increase satiety and reduce food intake in humans.

Both developed and developing countries are seeing increasing trends of obesity in people young and old. It is thought that satiety may play a role in the prevention of obesity by increasing satiety and reducing energy intake. We hypothesized that medium-chain triglycerides (MCT) would increase satiety and decrease food intake compared with conjugated linoleic acid (CLA) and a control oil. Nineteen healthy participants were tested on 3 separate occasions, where they consumed a beverage test breakfast containing (1) vegetable oil (control), (2) CLA, or (3) MCT. Participants self-requested an ad libitum sandwich buffet lunch. Time between meals, satiety from visual analog scales, energy intake at lunch, and intake for the rest of the day using weighed food diaries were measured. The results indicated that the time until a meal request was significantly different between the 3 meals (P=.016); however, there were no differences in intakes at the ad libitum lunch (P>.05). The CLA breakfast generated the greatest delay in meal time request. There was a difference between the control lipid compared with both the CLA and MCT for energy intake over the remainder of the test day and for total energy intake on the test day (P<.001 for both), with the CLA and MCT resulting in a lower intake than the control throughout the day. There were no significant differences in satiety from visual analog scale scores (P>.05). Both CLA and MCT increased satiety and reduced energy intake, indicating a potential role in aiding the maintenance of energy balance.

9- and 13-Hydroxy-octadecadienoic acids (9+13 HODE) are inversely related to granulocyte colony stimulating factor and IL-6 in runners after 2h running.

This study utilized a pro-inflammatory exercise mode to explore potential linkages between increases in 9- and 13-hydroxy-octadecadienoic acid (9+13 HODE) and biomarkers for inflammation, oxidative stress, and muscle damage. Male (N=10) and female (N=10) runners ran at ∼70% VO2max for 1.5h followed by 30min of downhill running (-10%). Blood samples were taken pre-run and immediately-, 1-h-, and 24-h post-run, and analyzed for 9+13 HODE, F2-isoprostanes, six cytokines, C-reactive protein (CRP), creatine kinase (CK), and myoglobin (MYO). Gender groups performed at comparable relative heart rate and oxygen consumption levels during the 2-h run. All outcome measures increased post-run (time effects, P⩽0.001), with levels near pre-run levels by 24h except for CRP, CK, MYO, and delayed onset of muscle soreness (DOMS). Plasma 9+13 HODE increased 314±38.4% post-run (P<0.001), 77.3±15.8% 1-h post-run (P<0.001), and 40.6±16.4% 24-h post-exercise (P=0.024), and F2-isoprostanes increased 50.8±8.9% post-run (P<0.001) and 19.0±5.3% 1-h post-run (P=0.006). Post-run increases were comparable between genders for all outcomes except for 9+13 HODE (interaction effect, P=0.024, post-run tending higher in females), IL-10 (P=0.006, females lower), and DOMS (P=0.029, females lower). The pre-to-post-run increase in 9+13 HODEs was not related to other outcomes except for plasma granulocyte colony stimulating factor (GCSF) (r=-0.710, P<0.001) and IL-6 (r=-0.457, P=0.043). Within the context of this study, exercise-induced increases in 9+13 HODEs tended higher in females, and were not related to increases in F2-isoprostanes, muscle damage, or soreness. The negative relationships to GCSF and IL-6 suggest a linkage between 9+13 HODES and exercise-induced neutrophil chemotaxis, degranulation, and inflammation.

LDL in patients with subclinical hypothyroidism shows increased lipid peroxidation.

BACKGROUND: Population-based studies have demonstrated that subclinical hypothyroidism (SCH) is an independent risk factor for atherosclerosis (OR = 1.9). However, this connection cannot be entirely explained by dyslipidemia accompanied by SCH. Lipid peroxidation also plays an important role in the development of atherosclerosis. In this study, we aimed to evaluate oxidative stress in SCH patients, as measured according to concentrations of hydroxy-octadecadienoic acids (HODEs) and hydroxy-eicosatetraenoic acids (HETEs) in both plasma and low density lipoproteins (LDL). SUBJECTS AND METHODS: The concentrations of HODEs and HETEs in both LDL and plasma were examined in euthyroid (n = 10), mild SCH (4.5 ≤ TSH < 10 mU/L, n = 10), and significant SCH (TSH ≥ 10 mU/L, n = 10) subjects, using a liquid chromatograph-electrospray ionization- mass spectrometer. Then, we explored the relationship among LDL oxidation, TSH levels, and carotid intima-media thickness (IMT), a biomarker of subclinical atherosclerosis. RESULTS: Serum LDL-C levels and mean-IMT in the significant SCH group were higher than in the euthyroid group (p < 0.05). The HODE and HETE concentrations clearly increased in the significant SCH patients compared with the euthyroid subjects, but there was no difference between the mild SCH and euthyroid groups. Among all subjects, linear and significant positive correlations were identified between TSH and mean-IMT after adjustment for confounding factors (r = 0.480, p = 0.018). Both 9-HODE (r = 0.376, p = 0.041) and 13-HODE (r = 0.447, p = 0.013) in LDL were linearly and positively correlated with TSH. The concentrations of HODEs (both 9-HODE and 13-HODE) in LDL were much higher in the thickened IMT group than in the normal IMT group (p = .017 and 0.015, respectively). HODEs in LDL were also positively associated with mean-IMT. CONCLUSIONS: Our findings showed that lipid peroxidation was higher in the significant SCH patients than in the euthyroid subjects, which suggested that qualitative as well as quantitative changes in serum lipids resulting from SCH may add to atherosclerosis risk.

Individual CLA Isomers, c9t11 and t10c12, Prevent Excess Liver Glycogen Storage and Inhibit Lipogenic Genes Expression Induced by High-Fructose Diet in Rats.

This study assessed the effects of individual conjugated linoleic acid isomers, c9t11-CLA and t10c12-CLA, on nonalcoholic fatty liver disease (NAFLD) and systemic endothelial dysfunction in rats fed for four weeks with control or high-fructose diet. The high-fructose diet hampered body weight gain (without influencing food intake), increased liver weight and glycogen storage in hepatocytes, upregulated expression of fatty acid synthase (FAS) and stearoyl-CoA desaturase-1 (SCD-1), and increased saturated fatty acid (SFA) content in the liver. Both CLA isomers prevented excessive accumulation of glycogen in the liver. Specifically, t10c12-CLA decreased concentration of serum triacylglycerols and LDL + VLDL cholesterol, increased HDL cholesterol, and affected liver lipid content and fatty acid composition by downregulation of liver SCD-1 and FAS expression. In turn, the c9t11-CLA decreased LDL+VLDL cholesterol in the control group and downregulated liver expression of FAS without significant effects on liver weight, lipid content, and fatty acid composition. In summary, feeding rats with a high-fructose diet resulted in increased liver glycogen storage, indicating the induction of gluconeogenesis despite simultaneous upregulation of genes involved in de novo lipogenesis. Although both CLA isomers (c9t11 and t10c12) display hepatoprotective activity, the hypolipemic action of the t10c12-CLA isomer proved to be more pronounced than that of c9t11-CLA.

Oral Absorption and Disposition of alpha-Linolenic, Rumenic and Vaccenic Acids After Administration as a Naturally Enriched Goat Dairy Fat to Rats.

Although there is extensive information describing the positive biological effects of conjugated linoleic acid and its main isomer rumenic acid (RA; C18:2 cis 9, trans 11), and alpha-linolenic acid (ALA) and vaccenic acid (TVA), data about their bioavailability are not available. In this work, we investigated the oral absorption and disposition of these fatty acids in Wistar rats. A naturally enriched goat dairy fat (EDF) was obtained by supplementing ruminant diets with oils or oilseeds rich in polyunsaturated fatty acids (PUFA). The EDF was administered orally (single dose of 3000 mg EDF/kg body weight equivalent to 153 mg TVA/kg body weight, 46 mg RA/kg body weight and 31 mg ALA/kg body weight), and serial blood and liver samples were collected and TVA, RA and ALA concentrations determined by GC/MS. The fatty acids TVA, RA and ALA were rapidly absorbed (t1/2a, 0.36, 0.66 and 0.76 h, respectively, for plasma) and slowly eliminated (t1/2ß, 17.04, 18.40 and 16.52 h, respectively, for plasma). The maximum concentration (C max) was detected in liver > plasma > erythrocyte. Our study shows that when orally administered EDF, its components TVA, RA and ALA were rapidly absorbed and distributed throughout the body by the blood circulation to exert systemic effects.

Association of foods enriched in conjugated linoleic acid (CLA) and CLA supplements with lipid profile in human studies: a systematic review and meta-analysis.

OBJECTIVE: The present study aimed to review the association of conjugated linoleic acid (CLA) consumption in two forms, foods enriched in CLA and CLA supplements, with serum lipid profile in human studies. DESIGN: Systematic review and meta-analysis. SETTING: Search process was conducted in PubMed, Cochrane Library, Google Scholar, Scopus and Science Direct. Clinical trials that investigated the association of CLA intakes either in the form of supplements or enriched foods with lipid profile in healthy adults were included. All outcomes were recorded as continuous variables, and the effect size was measured by analysis of the mean and standard deviation before and after the intervention for case and control groups. SUBJECTS: Healthy adult population. RESULTS: CLA supplementation was associated with a significant decrease in LDL cholesterol (mean difference = -0.218; 95% CI -0.358, -0.077; P = 0.002), a non-significant decrease in HDL cholesterol (mean difference = -0.051; 95% CI -0.188, 0.086; P = 0.468), a non-significant increase in total cholesterol (mean difference = 0.009; 95% CI -0.128, 0.146; P = 0.896) and a non-significant decrease in TAG (mean difference = -0.065; 95% CI -0.20, 0.07; P = 0.344). Foods enriched with CLA were associated with significantly decreased LDL cholesterol (mean difference = -0.231; 95% CI -0.438, -0.024; P = 0.028), non-significantly increased HDL-C (mean difference = 0.075; 95% CI -0.121, 0.270; P=0.455), non-significantly decreased total cholesterol (mean difference = -0.158; 95% CI -0.349, 0.042; P = 0.124) and non-significantly decreased TAG (mean difference = -0.078; 95% CI -0.274, 0.117; P = 0.433). CONCLUSIONS: According to our analysis, consumption of foods enriched with CLA or CLA supplements has favourable effects on LDL cholesterol levels.