In chronic fatigue syndrome, the decreased levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activation

There is now evidence that major depression is accompanied by decreased levels of omega3 poly-unsaturated fatty acids (PUFA), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). There is a strong comorbidity between major depression and chronic fatigue syndrome (CFS). The present study has been carried out in order to examine PUFA levels in CFS. In twenty-two CFS patients and 12 normal controls we measured serum PUFA levels using gas chromatography and mass spectrometry. We found that CFS was accompanied by increased levels of omega6 PUFAs, i.e. linoleic acid and arachidonic acid (AA), and mono-unsaturated fatty acids (MUFAs), i.e. oleic acid. The EPA/AA and total omega3/omega6 ratios were significantly lower in CFS patients than in normal controls. The omega3/omega6 ratio was significantly and negatively correlated to the severity of illness and some items of the FibroFatigue scale, i.e. aches and pain, fatigue and failing memory. The severity of illness was significantly and positively correlated to linoleic and arachidonic acid, oleic acid, omega9 fatty acids and one of the saturated fatty acids, i.e. palmitic acid. In CFS subjects, we found significant positive correlations between the omega3/omega6 ratio and lowered serum zinc levels and the lowered mitogen-stimulated CD69 expression on CD3+, CD3+ CD4+, and CD3+ CD8+ T cells, which indicate defects in early T cell activation. The results of this study show that a decreased availability of omega3 PUFAs plays a role in the pathophysiology of CFS and is related to the immune pathophysiology of CFS. The results suggest that patients with CFS should respond favourably to treatment with--amongst other things--omega3 PUFAs, such as EPA and DHA.     

Lipid peroxidation of poly-unsaturated fatty acids in normal and obese adipose tissues

Adipose tissues function as the primary storage compartment of fatty acids and as an endocrine organ that affects peripheral tissues. Many of adipose tissue-derived factors, often termed adipokines, have been discovered in recent years. The synthesis and secretion of these factors vary in different depots of adipose tissues. Excessive lipid accumulation in adipocytes induces inflammatory processes by up-regulating the expression and release of pro-inflammatory cytokines. In addition, activated macrophages in the obese adipose tissue release inflammatory cytokines. Adipose tissue inflammation has also been linked to an enhanced metabolism of polyunsaturated fatty acids (PUFAs). The non-enzymatic peroxidation of PUFAs and of their 12/15-lipoxygenase-derived hydroperoxy metabolites leads to the generation of the reactive aldehyde species 4-hydroxyalkenals. This review shows that 4-hydroxyalkenals, in particular 4-hydroxynonenal, play a key role in lipid storage homeostasis in normal adipocytes. Nonetheless, in the obese adipose tissue an increased production of 4-hydroxyalkenals contributes to the inflamed phenotype.     

In silico evidence for gluconeogenesis from fatty acids in humans

The question whether fatty acids can be converted into glucose in humans has a long standing tradition in biochemistry, and the expected answer is “No”. Using recent advances in Systems Biology in the form of large-scale metabolic reconstructions, we reassessed this question by performing a global investigation of a genome-scale human metabolic network, which had been reconstructed on the basis of experimental results. By elementary flux pattern analysis, we found numerous pathways on which gluconeogenesis from fatty acids is feasible in humans. On these pathways, four moles of acetyl-CoA are converted into one mole of glucose and two moles of CO₂. Analyzing the detected pathways in detail we found that their energetic requirements potentially limit their capacity. This study has many other biochemical implications: effect of starvation, sports physiology, practically carbohydrate-free diets of inuit, as well as survival of hibernating animals and embryos of egg-laying animals. Moreover, the energetic loss associated to the usage of gluconeogenesis from fatty acids can help explain the efficiency of carbohydrate reduced and ketogenic diets such as the Atkins diet.     

Multiple routes of chemosensitivity to free fatty acids in humans

Selected free fatty acids (FFAs) are documented effective somatosensory and olfactory stimuli whereas gustatory effects are less well established. This study examined orthonasal olfactory, retronasal olfactory, nasal irritancy, oral irritancy, gustatory, and multimodal threshold sensitivity to linoleic, oleic, and stearic acids. Sensitivity to oxidized linoleic acid was also determined. Detection thresholds were obtained using a three-alternative, forced-choice, ascending concentration presentation procedure. Participants included 22 healthy, physically fit adults sensitive to 6-n-propylthiouracil. Measurable thresholds were obtained for all FFAs tested and in 96% of the trials. Ceiling effects were observed in the remaining trials. Greater sensitivity was observed for multimodal stimulation and lower sensitivity for retronasal stimulation. There were no statistically significant correlations for linoleic acid thresholds between different modalities, suggesting that each route of stimulation contributes independently to fat perception. In summary, 18-carbon FFAs of varying saturation are detected by multiple sensory systems in humans.     

In vivo investigation of the placental transfer of (13)C-labeled fatty acids in humans

Placental fatty acid transfer in humans in vivo was studied using stable isotopes. Four pregnant women undergoing cesarean section received 4 h before delivery an oral dose of [(13)C]palmitic acid (PA), [(13)C]oleic acid (OA), [(13)C]linoleic acid (LA), and [(13)C]docosahexaenoic acid (DHA). Maternal blood samples were collected at -4 h (basal), -3 h, -2 h, -1 h, 0 h, and +1 h relative to time of cesarean section. At the time of birth, venous cord blood and placental tissue were collected. Fatty acid composition was determined by gas-liquid chromatography and isotopic enrichment by gas chromatography-combustion-isotope ratio mass spectrometry. (13)C-enrichment of fatty acids in the nonesterified fatty acids (NEFA) of cord plasma tended to be higher than in NEFA of placenta, with statistically significant differences for the nonesterified OA and DHA ([(13)C]PA, 0.024 +/- 0.011 vs. 0.001 +/- 0.001; [(13)C]OA, 0.042 +/- 0.008 vs. 0.005 +/- 0.003; [(13)C]LA, 0.038 +/- 0.010 vs. 0.008 +/- 0.002; [(13)C]DHA, 0.059 +/- 0.009 vs. 0.010 +/- 0.003). The ratio of tracer fatty acid concentrations of placenta to maternal plasma was significantly higher for [(13)C]DHA than for the other fatty acids ([(13)C]PA, 7.1 +/- 1%; [(13)C]OA, 3.8 +/- 0.4%; [(13)C]LA, 9.2 +/- 1.3%; [(13)C]DHA, 25.9 +/- 3.4%). These results suggest that only a part of the placental NEFA participated in fatty acid transfer, and that the placenta showed a preferential accretion of DHA relative to the other fatty acids.     

Regional uptake of meal fatty acids in humans

Two protocols were performed to study meal fatty acid metabolism. In protocol 1, 14 patients scheduled for elective intra-abdominal surgery (11 undergoing bariatric surgery for severe obesity) consumed a meal containing [3H]triolein in the evening before surgery. This allowed us to measure adipose tissue lipid specific activity (SA) in mesenteric and omental, deep and superficial abdominal subcutaneous adipose tissue. Intra-abdominal adipose tissue lipid SA was greater than subcutaneous lipid SA. There were no significant differences between mesenteric and omental or between deep and superficial abdominal subcutaneous adipose tissue. In protocol 2, meal fatty acid oxidation and uptake into subcutaneous and omental adipose tissue ([3H]triolein) were measured in six normal, healthy volunteers. Meal fatty acid oxidation (3H2O generation) plus that remaining in plasma ( approximately 1%) plus uptake into upper body subcutaneous, lower body subcutaneous, and visceral fat allowed us to account for 98 +/- 6% of meal fatty acids 24 h after meal ingestion. We conclude that omental fat is a good surrogate for visceral fat and that abdominal subcutaneous fat depots are comparable with regard to meal fatty acid metabolic studies. Using [3H]triolein, we were able to account for virtually 100% of meal fatty acids 24 h after meal ingestion. These results support the meal fatty acid tracer model as a way to study the metabolic fate of dietary fat.     

Novel experimental protocol to increase specific plasma nonesterified fatty acids in humans

This study reports a novel protocol to increase plasma monounsaturated, polyunsaturated, and saturated nonesterified fatty acids (NEFA) in eight healthy volunteers (age 29-54 yr, body mass index 23-26 kg/m(2)). This was achieved by feeding small boluses of fat at different time points (35 g at 0 min and 8 g at 30, 60, 90, 120, 150, 180, and 210 min) in combination with a continuous low-dose heparin infusion. Olive oil, safflower oil, or palm stearin were used to increase monounsaturated, polyunsaturated, or saturated NEFAs, respectively. Plasma NEFA concentrations were increased for 2 h, when fat and heparin were given (olive oil: 745 +/- 35 micromol/l; safflower oil: 609 +/- 37 micromol/l, and palm stearin: 773 +/- 38 micromol/l) compared with the control test (no fat and no heparin: 445 +/- 41 micromol/l). During the heparin infusion, 18:1 n-9 was the most abundant fatty acid for the olive oil test compared with 18:2 n-6 for the safflower oil test and 16:0 for the palm stearin test (P < 0.01). The method described here successfully increases several types of plasma NEFA concentrations and could be used to investigate differential effects of elevated individual NEFAs on metabolic processes.     

Serum phospholipid fatty acids, adipose tissue, and metabolic markers in obese adolescents

Objective: Fatty acid (FA) composition has a role in adipogenesis. The objective was to study serum phospholipid (PL) FAs in adolescents and their relation to abdominal adipose tissue (AT) compartments and metabolic markers. Research Methods and Procedures: Abdominal AT was measured by magnetic resonance imaging and FA pattern was determined in serum PL of 10 obese adolescents (5 females), median age 12.0 years (range, 10.4 to 16.4) and BMI 30.7 (26.8 to 40.4), and 15 lean control subjects (9 females), median age 12.6 years (range, 11.3 to 15.4), and BMI 19.5 (17.1 to 23.4). Results: Obese adolescents had relatively higher levels of saturated FA (SFA) and nervonic acid compared with controls. Serum PL concentration of n‐3 polyunsaturated fatty acids (PUFA) was lower in the obese vs. lean females (p = 0.01), including docosahexaenoic acid (DHA) (p = 0.01). The ratios of arachidonic acid to DHA and total n‐6/n‐3 FA were increased in obese children (p = 0.02 and 0.01, respectively). n‐3 PUFAs were inversely correlated to all subcutaneous AT compartments except visceral AT. The homeostasis model assessment index of β‐cell function related inversely to DHA concentration (p = 0.03). All changes were more marked in the females. Discussion: Serum FA pattern in obese adolescents differed significantly from that in age‐matched lean controls, reflecting a decrease in n‐3 PUFA, especially DHA, and an increase in SFA. The subcutaneous AT, but not visceral AT, correlated to the changes in PUFA and SFA, suggesting an abnormal essential FA metabolism in obese adolescents.     

棉蚜种群季节性变异的生态条件

研究棉蚜在不同温度下取食不同生育期棉叶后种群的变动情况。通过Weibull函数模拟、生命表分析和高氏距离分析比较表明,无论在苗期和蕾期,随着渐度的升高棉蚜种群的死亡高峰日均提前,世代寿命明显缩短;然而,在20-25℃范围内,相同温度时棉蚜生活在棉花蕾期叶上的繁殖力明显高于苗期叶上的繁殖力。在30℃时繁殖力普遍明显下降,温度20-25℃最适于棉蚜的生长与繁殖。且棉花殖生长期比营养生长期更适于棉蚜的生存和繁殖,温度与棉花生育期都是导致苗蚜与伏蚜生长与繁殖差异的外界因素。     

Polyunsaturated fatty acids in zooplankton: variation due to taxonomy and trophic position

1. Food quality has major effects on the transfer of energy and matter in food webs, and essential long‐chained polyunsaturated fatty acids (PUFAs) can affect the quality of phytoplankton as food. In a study of oligotrophic lakes in north‐western Sweden, we investigated the fatty acid composition of four planktonic cladocerans and two calanoid copepods, representing herbivorous and carnivorous species. We also collected seston samples. 2. The proportions of long‐chain PUFAs in the organisms increased with their increasing trophic position. Thus, both their quality as food for other organisms, as well as their requirement for fatty acids (FAs), differed among taxa and depended on their trophic position. 3. We found taxon‐specific differences in the FA composition of zooplankton that were not related to sestonic FA composition. This implies that the variation in zooplankton FA composition is constrained by phylogenetic origin, life history characteristics, or both. 4. The cladoceran taxa contained 12–23% eicosapentaenoic acid (EPA) but only 0.9–2.1% docosahexaenoic acid (DHA) of the total FA content. In contrast, the calanoid copepods contained 7–11% EPA and 14–21% DHA. Thus, our results show that differences in the PUFA content among zooplankton species could have repercussions for both food web structure and function.     

Kinetics of intramuscular triglyceride fatty acids in exercising humans.

A pulse ([(14)C]palmitate)-chase ([(3)H]palmitate) approach was used to study intramuscular triglyceride (imTG) fatty acid and plasma free fatty acid (FFA) kinetics during exercise at approximately 45% peak O(2) consumption in 12 adults. Vastus lateralis muscle was biopsied before and after 90 min of bicycle exercise; (3)H(2)O production, breath (14)CO(2) excretion and lipid oxidation (indirect calorimetry) rates were measured during exercise. Results: during exercise, 8.2+/-1.2 and 8.4+/-0.7 micromol x kg(-1) x min(-1) of imTG fatty acids and plasma FFA, respectively, were oxidized according to isotopic measurements. The sum of these two values was not different (P = 0.6) from lipid oxidation by indirect calorimetry (15.4 +/-1.6 micromol x kg(-1) x min(-1)); the isotopic and indirect calorimetry values were correlated (r = 0.79, P<0.005). During exercise, imTG turnover rate was 0.32+/-0.07%/min (6.0+/-2.0 micromol of imTG x kg wet muscle(-1) x min(-1)) and plasma FFA were incorporated into imTG at a rate of 0.7+/-0.1 micromol x kg wet muscle(-1) x min(-1). The imTG pool size did not change during exercise. This pulse-chase, dual tracer appears to be a reasonable approach to measure oxidation and synthesis kinetics of imTG.     

Seasonal variation in triacylglyceride fatty acids of dwarf mistletoes

Fatty acids in the triacylglyceride fraction of three species of dwarf mistletoe (Arceuthobium, Viscaceae) showed considerable seasonal variation in proportions of saturated acids and some differences in chain length for those fatty acids. Early summer aerial shoot tissue contained 34–49% saturated fatty acids, while the same species in late October had only 8–15% saturated fatty acids. Fatty acids with a chain length of C₂₀ or greater comprised 18–25% of the total in late June but only 1.5–6.4% in the autumn. Three other species analysed in only one season showed similar saturated fatty acids, and chain length patterns were also parallel to the seasonally varying species analysed in the same season. The ratio of linolenic to oleic acid remained constant with season but linolenic acid increased from less than 1% in June to 7–8% in October samples.     

Metabolism and functional effects of plant-derived omega-3 fatty acids in humans

Alpha-linolenic acid (ALA) is an essential fatty acid and the substrate for the synthesis of longer-chain, more unsaturated ω-3 fatty acids, eicosapentaenoic acid (EPA), docosapentaenoic acid and docosahexaenoic acid (DHA). EPA and DHA are associated with human health benefits. The primary source of EPA and DHA is seafood. There is a need for sustainable sources of biologically active ω-3 fatty acids. Certain plants contain high concentrations of ALA and stearidonic acid (SDA). Here we review the literature on the metabolism of ALA and SDA in humans, the impact of increased ALA and SDA consumption on concentrations of EPA and DHA in blood and cell lipid pools, and the extent to which ALA and SDA might have health benefits. Although it is generally considered that humans have limited capacity for conversion of ALA to EPA and DHA, sex differences in conversion to DHA have been identified. If conversion of ALA to EPA and DHA is limited, then ALA may have a smaller health benefit than EPA and DHA. SDA is more readily converted to EPA and appears to offer better potential for health improvement than ALA. However, conversion of both ALA and SDA to DHA is limited in most humans.     

Mechanism of insulin-stimulated clearance of plasma nonesterified fatty acids in humans

Insulin increases plasma nonesterified fatty acid (NEFA) clearance in humans, but whether this is independent of change in plasma NEFA appearance is currently unknown. Nine nondiabetic men (age: 28+/-3 yr, body mass index: 27.2+/-1.7 kg/m2) underwent euglycemic clamps to maintain low (LINS) vs. high (HINS) physiological insulin levels for 6 h. An intravenous infusion of heparin+Intralipid (HI) was performed during 4 of the 6 h of the clamps (in the last 4 h at LINS and in the first 4 h at HINS), whereas saline infusion (SAL) was administered in the remaining 2 h to modulate plasma NEFA levels independently of plasma insulin levels. Four experimental conditions were obtained in each individual: LINS with saline (LINS/SAL) and with HI infusion (LINS/HI) and HINS with saline (HINS/SAL) and with HI infusion (HINS/HI). Plasma palmitate appearance during HINS/SAL was lower than during the three other experimental conditions (P<0.05). In contrast, plasma linoleate appearance, as expected, was increased by HI independently of insulin level (P<0.02). Plasma palmitate clearance during HINS/SAL was higher than LINS/SAL and LINS/HI (P<0.008), and this increase was blunted during HINS/HI. We observed a linear decrease in plasma palmitate clearance with increasing plasma NEFA appearance independent of insulin levels. Plasma NEFA levels increased exponentially with increase in plasma NEFA appearance. We conclude that insulin stimulates plasma NEFA clearance by reducing the endogenous appearance rate of NEFA. The relationship between plasma NEFA level and appearance rate is nonlinear.