Effect of abomasal glucose infusion on plasma concentrations of gut peptides in periparturient dairy cows

Six Holstein cows fitted with ruminal cannulas and permanent indwelling catheters in the portal vein, hepatic vein, mesenteric vein, and an artery were used to study the effects of abomasal glucose infusion on splanchnic plasma concentrations of gut peptides. The experimental design was a randomized block design with repeated measurements. Cows were assigned to one of 2 treatments: control or infusion of 1,500 g of glucose/d into the abomasum from the day of parturition to 29 d in milk. Cows were sampled 12 ± 6 d prepartum and at 4, 15, and 29 d in milk. Concentrations of glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1(7–36) amide, and oxyntomodulin were measured in pooled samples within cow and sampling day, whereas active ghrelin was measured in samples obtained 30 min before and after feeding at 0800 h. Postpartum, dry matter intake increased at a lower rate with infusion compared with the control. Arterial, portal venous, and hepatic venous plasma concentrations of the measured gut peptides were unaffected by abomasal glucose infusion. The arterial, portal venous, and hepatic venous plasma concentrations of glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1(7–36) amide increased linearly from 12 d prepartum to 29 d postpartum. Plasma concentrations of oxyntomodulin were unaffected by day relative to parturition. Arterial and portal venous plasma concentrations of ghrelin were lower postfeeding compared with prefeeding concentrations. Arterial plasma concentrations of ghrelin were greatest prepartum and lowest at 4 d postpartum, giving a quadratic pattern of change over the transition period. Positive portal venous-arterial and hepatic venous–arterial concentration differences were observed for glucagon-like peptide 1(7–36) amide. A negative portal venous–arterial concentration difference was observed for ghrelin pre-feeding. The remaining portal venous–arterial and hepatic venous–arterial concentration differences of gut peptides did not differ from zero. In conclusion, increased postruminal glucose supply to postpartum transition dairy cows reduced feed intake relative to control cows, but did not affect arterial, portal venous, or hepatic venous plasma concentrations of gut peptide hormones. Instead, gut peptide plasma concentrations increased as lactation progressed. Thus, the lower feed intake of postpartum dairy cows receiving abomasal glucose infusion was not attributable to changes in gut peptide concentrations.

Prolonged effects of modified sham feeding on energy substrate mobilization

Background: Vagal stimulation in response to nutrients is reported to elicit an array of digestive and endocrine responses, including an alteration in postprandial lipid metabolism. Objective: The objective of this study was to assess whether neural stimulation could alter hormone and substrate metabolism during the late postprandial phase, with implications for body fat mobilization. Design: Vagal stimulation was achieved by using the modified sham feeding (MSF) technique, in which nutrients are chewed and tasted but not swallowed. Ten healthy subjects were studied on 3 separate occasions, 4 wk apart. Five hours after a high-fat breakfast (56 g fat), the subjects were given 1 of 3 test meals allocated in random order: water, a lunch containing a modest amount of fat (38 g), or MSF (38 g fat). Blood was collected for 3 h poststimulus for hormone and metabolite analyses. Results: Plasma insulin and pancreatic polypeptide concentrations peaked at 250% and 209% of baseline concentrations within 15 min of MSF. The plasma glucose concentration increased significantly (P = 0.038) in parallel with the changes observed in the plasma insulin concentration. The nonesterified fatty acid concentration was significantly suppressed (P = 0.006); maximum suppression occurred at a mean time of 114 min after MSF. This fall in nonesterified fatty acid was accompanied by a fall in the plasma glucagon concentration from 122 to 85 pmol/L (P = 0.018) at a mean time of 113 min after MSF. Conclusions: Effects on substrate metabolism after MSF in the postprandial state differ from those usually reported in the postabsorptive state. The effects of MSF were prolonged beyond the period of the cephalic response and these may be relevant for longer-term metabolic regulation.

Inter-relationships between small, dense low-density lipoprotein (LDL), plasma triacylglycerol and LDL apoprotein B in an atherogenic lipoprotein phenotype in free-living subjects

A predominance of small, dense low-density lipoprotein (LDL) is a major component of an atherogenic lipoprotein phenotype, and a common, but modifiable, source of increased risk for coronary heart disease in the free-living population. While much of the atherogenicity of small, dense LDL is known to arise from its structural properties, the extent to which an increase in the number of small, dense LDL particles (hyper-apoprotein B) contributes to this risk of coronary heart disease is currently unknown. This study reports a method for the recruitment of free-living individuals with an atherogenic lipoprotein phenotype for a fish-oil intervention trial, and critically evaluates the relationship between LDL particle number and the predominance of small, dense LDL. In this group, volunteers were selected through local general practices on the basis of a moderately raised plasma triacylglycerol (triglyceride) level (>1.5 mmol/l) and a low concentration of high-density-lipoprotein cholesterol (<1.1 mmol/l). The screening of LDL subclasses revealed a predominance of small, dense LDL (LDL subclass pattern B) in 62% of the cohort. As expected, subjects with LDL subclass pattern B were characterized by higher plasma triacylglycerol and lower high-density lipoprotein cholesterol (<1.1 mmol/l) levels and, less predictably, by lower LDL cholesterol and apoprotein B levels (P<0.05; LDL subclass A compared with subclass B). While hyper-apoprotein B was detected in only five subjects, the relative percentage of small, dense LDL-III in subjects with subclass B showed an inverse relationship with LDL apoprotein B (r=-0.57; P<0.001), identifying a subset of individuals with plasma triacylglycerol above 2.5 mmol/l and a low concentration of LDL almost exclusively in a small and dense form. These findings indicate that a predominance of small, dense LDL and hyper-apoprotein B do not always co-exist in free-living groups. Moreover, if coronary risk increases with increasing LDL particle number, these results imply that the risk arising from a predominance of small, dense LDL may actually be reduced in certain cases when plasma triacylglycerol exceeds 2.5 mmol/l.

A comparison of reverse osmosis, nanofiltration and ultrafiltration as concentration processes for skim milk prior to drying

Skim milk was concentrated by reverse osmosis (RO), nanofiltration (NF) and ultrafiltration (UF) and the retentates were spray-dried. The resulting powders were reconstituted to 25% TS and sterilised to evaluate their heat stability. Reverse osmosis led to maximum retention of calcium, a fall in pH for its retentate and its reconstituted powder. All RO powders produced a weak gel on heating. Some calcium was lost during NF and a greater amount during UF. Their resulting reconstituted powders had a higher pH than those produced by RO. Powders produced by UF showed poor heat stability. Only one powder produced by NF showed good heat stability. This could be improved by addition of stabilisers at appropriate addition rates.

Last Glacial Maximum CO2 and δ13C successfully reconciled

During the Last Glacial Maximum (LGM, ∼21,000 years ago) the cold climate was strongly tied to low atmospheric CO2 concentration (∼190 ppm). Although it is generally assumed that this low CO2 was due to an expansion of the oceanic carbon reservoir, simulating the glacial level has remained a challenge especially with the additional δ13C constraint. Indeed the LGM carbon cycle was also characterized by a modern-like δ13C in the atmosphere and a higher surface to deep Atlantic δ13C gradient indicating probable changes in the thermohaline circulation. Here we show with a model of intermediate complexity, that adding three oceanic mechanisms: brine induced stratification, stratification-dependant diffusion and iron fertilization to the standard glacial simulation (which includes sea level drop, temperature change, carbonate compensation and terrestrial carbon release) decreases CO2 down to the glacial value of ∼190 ppm and simultaneously matches glacial atmospheric and oceanic δ13C inferred from proxy data. LGM CO2 and δ13C can at last be successfully reconciled.

PPARγ2 gene Pro12Ala and PPARα gene Leu162Val single nucleotide polymorphisms interact with dietary intake of fat in determination of plasma lipid concentrations

Background/Aims: The peroxisome proliferator-activated receptors (PPARs) are transcriptional regulators of lipid metabolism, activated by unsaturated fatty acids. We investigated independent and interactive effects of PPARγ2 gene PPARG Pro12Ala (rs1801282) andPPARαgene PPARA Leu162Val (rs1800206) genotypes with dietary intake of fatty acids on concentrations of plasma lipids in subjects of whom 47.5% had metabolic syndrome. Methods: The RISCK study is a parallel design, randomised controlled trial. Plasma lipids were quantified at baseline after a 4-week high saturated fatty acids diet and after three parallel 24-week interventions with reference (high saturated fatty acids), high monounsaturated fatty acids and low-fat diets. Single nucleotide polymorphisms were genotyped in 466 subjects. Results: At baseline, the PPARG Ala12allele was associated with increased plasma total cholesterol (n = 378; p = 0.04), LDL cholesterol (p = 0.05) and apoB (p =0.05) after adjustment for age, gender and ethnicity. At baseline, PPARA Leu162Val × PPARG Pro12Ala genotype interaction did not significantly influence plasma lipid concentrations. After dietary intervention, gene-gene interaction significantly influenced LDL cholesterol (p =0.0002) and small dense LDL as a proportion of LDL (p = 0.005) after adjustments. Conclusions: Interaction between PPARG Pro12Ala and PPARA Leu162Valgenotypes may influence plasma LDL cholesterol concentration and the proportion as small dense LDL after a high monounsaturated fatty acids diet.

A period 2 genetic variant interacts with plasma SFA to modify plasma lipid concentrations in adults with metabolic syndrome

Genetic variants of Period 2 (PER2), a circadian clock gene, have been linked to metabolic syndrome (MetS). However, it is still unknown whether these genetic variants interact with the various types of plasma fatty acids. This study investigated whether common single nucleotide polymorphisms (SNPs) in the PER2 locus (rs934945 and rs2304672) interact with various classes of plasma fatty acids to modulate plasma lipid metabolism in 381 participants with MetS in the European LIPGENE study. Interestingly, the rs2304672 SNP interacted with plasma total SFA concentrations to affect fasting plasma TG, TG-rich lipoprotein (TRL-TG), total cholesterol, apoC-II, apoB, and apoB-48 concentrations (P-interaction < 0.001–0.046). Carriers of the minor allele (GC+GG) with the highest SFA concentration (>median) had a higher plasma TG concentration (P = 0.001) and higher TRL-TG (P < 0.001) than the CC genotype. In addition, participants carrying the minor G allele for rs2304672 SNP and with a higher SFA concentration (>median) had higher plasma concentrations of apo C-II (P < 0.001), apo C-III (P = 0.009), and apoB-48 (P = 0.028) compared with the homozygotes for the major allele (CC). In summary, the rs2304672 polymorphism in the PER2 gene locus may influence lipid metabolism by interacting with the plasma total SFA concentration in participants with MetS. The understanding of these gene-nutrient interactions could help to provide a better knowledge of the pathogenesis in MetS.

Effect on components of the intestinal microflora and plasma neuropeptide levels of feeding Lactobacillus delbrueckii, Bifidobacterium lactis, and inulin to adult and elderly rats

The aim of this study was to compare the effects of the mixture of Lactobacillus delbrueckii subsp. rhamnosus strain GG, Bifidobacterium lactis Bb12, and inulin on intestinal populations of lactobacilli, bifidobacteria, and enterobacteria in adult and elderly rats fed the same (in quality and quantity) diet. The portal plasma levels of two neuropeptides, neuropeptide Y (NPY) and peptide YY (PYY), were also evaluated to assess the physiological consequences of the synbiotic treatment for the gastrointestinal (GI) tracts of rats of different ages. Adult (n = 24) and elderly (n = 24) male rats were fed the AIN-93 M maintenance diet. After 2 weeks of adaptation, the diet of 12 rats of each age group was supplemented with 8% inulin and with strains GG and Bb12 to provide 2.2 x 10(9) CFU of each strain g(-1) of the diet. Blood and different regions of the GI tract were sampled from all rats after 21 days of the treatment. Treatment with the mixture of strain GG, strain BB12, and inulin induced significantly different changes in the numbers of lactobacilli, bifidobacteria, and enterobacteria of the stomach, small intestine, cecum, and colon microflora. Moreover, the GG, BB12, and inulin mixture increased the concentrations of NPY and PYY for adult rats. For the elderly animals, the PYY concentration was not changed, while the NPY concentration was decreased by treatment with the GG, BB12, and inulin mixture. The results of the present study indicate that the physiological status of the GI tract, and not just diet, has a major role in the regulation of important groups of the GI bacteria community, since even the outcome of the dietary modification with synbiotics depends on the ages of the animals.

Recycling and resensitization of the neurokinin 1 receptor: influence of agonist concentration and Rab GTPases

Substance P (SP) induces endocytosis and recycling of the neurokinin 1 receptor (NK1R) in endothelial cells and spinal neurons at sites of inflammation and pain, and it is thus important to understand the mechanism and function of receptor trafficking. We investigated how the SP concentration affects NK1R trafficking and determined the role of Rab GTPases in trafficking. NK1R trafficking was markedly influenced by the SP concentration. High SP (10 nM) induced translocation of the NK1R and beta-arrestin 1 to perinuclear sorting endosomes containing Rab5a, where NK1R remained for >60 min. Low SP (1 nM) induced translocation of the NK1R to early endosomes located immediately beneath the plasma membrane that also contained Rab5a and beta-arrestin 1, followed by rapid recycling of the NK1R. Overexpression of Rab5a promoted NK1R translocation to perinuclear sorting endosomes, whereas the GTP binding-deficient mutant Rab5aS34N caused retention of the NK1R in superficial early endosomes. NK1R translocated from superficial early endosomes to recycling endosomes containing Rab4a and Rab11a, and Rab11aS25N inhibited NK1R recycling. Rapid NK1R recycling coincided with resensitization of SP-induced Ca2+ mobilization and with the return of surface SP binding sites. Resensitization was minimally affected by inhibition of vacuolar H(+)-ATPase and phosphatases but was markedly suppressed by disruption of Rab4a and Rab11a. Thus, whereas beta-arrestins mediate NK1R endocytosis, Rab5a regulates translocation between early and sorting endosomes, and Rab4a and Rab11a regulate trafficking through recycling endosomes. We have thus identified a new function of Rab5a as a control protein for directing concentration-dependent trafficking of the NK1R into different intracellular compartments and obtained evidence that Rab4a and Rab11a contribute to G-protein-coupled receptor recycling from early endosomes.

Climate and CO2 controls on global vegetation distribution at the last glacial maximum: analysis based on palaeovegetation data, biome modelling and palaeoclimate simulations.

The global vegetation response to climate and atmospheric CO2 changes between the last glacial maximum and recent times is examined using an equilibrium vegetation model (BIOME4), driven by output from 17 climate simulations from the Palaeoclimate Modelling Intercomparison Project. Features common to all of the simulations include expansion of treeless vegetation in high northern latitudes; southward displacement and fragmentation of boreal and temperate forests; and expansion of drought-tolerant biomes in the tropics. These features are broadly consistent with pollen-based reconstructions of vegetation distribution at the last glacial maximum. Glacial vegetation in high latitudes reflects cold and dry conditions due to the low CO2 concentration and the presence of large continental ice sheets. The extent of drought-tolerant vegetation in tropical and subtropical latitudes reflects a generally drier low-latitude climate. Comparisons of the observations with BIOME4 simulations, with and without consideration of the direct physiological effect of CO2 concentration on C3 photosynthesis, suggest an important additional role of low CO2 concentration in restricting the extent of forests, especially in the tropics. Global forest cover was overestimated by all models when climate change alone was used to drive BIOME4, and estimated more accurately when physiological effects of CO2 concentration were included. This result suggests that both CO2 effects and climate effects were important in determining glacial-interglacial changes in vegetation. More realistic simulations of glacial vegetation and climate will need to take into account the feedback effects of these structural and physiological changes on the climate.

Plasma free fatty acids do not provide the link between obesity and insulin resistance or β-cell dysfunction: results of the Reading, Imperial, Surrey, Cambridge, Kings (RISCK) study

Aims To investigate the relationship between adiposity and plasma free fatty acid levels and the influence of total plasma free fatty acid level on insulin sensitivity and β-cell function. Methods An insulin sensitivity index, acute insulin response to glucose and a disposition index, derived from i.v. glucose tolerance minimal model analysis and total fasting plasma free fatty acid levels were available for 533 participants in the Reading, Imperial, Surrey, Cambridge, Kings study. Bivariate correlations were made between insulin sensitivity index, acute insulin response to glucose and disposition index and both adiposity measures (BMI, waist circumference and body fat mass) and total plasma free fatty acid levels. Multivariate linear regression analysis was performed, controlling for age, sex, ethnicity and adiposity. Results After adjustment, all adiposity measures were inversely associated with insulin sensitivity index (BMI: β = −0.357; waist circumference: β = −0.380; body fat mass: β = −0.375) and disposition index (BMI: β = −0.215; waist circumference: β = −0.248; body fat mass: β = −0.221) and positively associated with acute insulin response to glucose [BMI: β = 0.200; waist circumference: β = 0.195; body fat mass β = 0.209 (P values <0.001)]. Adiposity explained 13, 4 and 5% of the variation in insulin sensitivity index, acute insulin response to glucose and disposition index, respectively. After adjustment, no adiposity measure was associated with free fatty acid level, but total plasma free fatty acid level was inversely associated with insulin sensitivity index (β = −0.133), acute insulin response to glucose (β = −0.148) and disposition index [β = −0.218 (P values <0.01)]. Plasma free fatty acid concentration accounted for 1.5, 2 and 4% of the variation in insulin sensitivity index, acute insulin response to glucose and disposition index, respectively. Conclusions Plasma free fatty acid levels have a modest negative association with insulin sensitivity, β-cell secretion and disposition index but no association with adiposity measures. It is unlikely that plasma free fatty acids are the primary mediators of obesity-related insulin resistance or β-cell dysfunction.

The modelled occurrence of non-thermal plasma in the ionospheric F-region and the possible consequences for ion outflows into the magnetosphere

A global, time-dependent, three-dimensional, coupled ionosphere-thermosphere model is used to predict the spatial distribution of non-thermal plasma in the F-layer. It is shown that, even for steady-state conditions with Kp as low as 3, the difference between the ion and neutral velocities often exceeds the neutral thermal speed by a factor, D', which can be as large as 4. Theoretically, highly non-Maxwellian, and probably toroidal, ion velocity distributions are expected when D' exceeds about 1.5. The lack of response of the neutral winds to sunward ion drifts in the dawn sector of the auroral oval cause this to be the region most likely to contain toroidal distributions. The maximum in D' is found in the throat region of the convection pattern, where the strong neutral winds of the afternoon sector meet the eastward ion flows of the morning sector. These predictions are of interest, not only to radar scientists searching for non-thermal ionospheric plasma, but also as one possible explanation of the initial heating and upward flows of ions in the cleft ion fountain and nightside auroral oval, both of which are a major source of plasma for the magnetosphere.

Field-aligned plasma flow in the quiet, mid-latitude ionosphere deduced from topside soundings

A method for quantifying diffusive flows of O+ ions in the topside ionosphere from satellite soundings is described. A departure from diffusive equilibrium alters the shape of the plasma scale-height profile near the F2-peak where ion-neutral frictional drag is large. The effect enables the evaluation of , the field-aligned flux of O+ ions relative to the neutral oxygen atom gas, using MSIS model values for the neutral thermospheric densities and temperature. Upward flow values are accurate to within about 10%, the largest sources of error being the MSIS prediction for the concentration of oxygen atoms and the plasma temperature gradient deduced from the sounding. Downward flux values are only determined to within 20%. From 60,000 topside soundings, taken at the minimum and rising phase of the solar cycle, a total of 1098 mean scale-height profiles are identified for which no storm sudden commencement had occurred in the previous 12 days and for which Kp was less than 2o, each mean profile being an average of about six soundings. A statistical study ofdeduced from these profiles shows the diurnal cycle of O+ flow in the quiet, topside ionosphere at mid-latitudes and its seasonal variations. The differences betweenand ion flux observations from incoherent scatter radars are considered using the meridional thermospheric winds predicted by a global, three-dimensional model. The mean interhemispheric flow from summer to winter is compared with predictions by a numerical model of the protonospheric coupling of conjugate ionospheres for up to 6 days following a geomagnetic storm. The observed mean (of order 3 × 1016 ions day−1 along a flux tube of area 1 m2 at 1000 km) is larger than predicted for day 6 and the suggested explanation is a decrease in upward flows from the winter, daytime ionosphere between the sixth and twelfth days.

A novel combined biomarker including plasma carotenoids, vitamin C, and ferric reducing antioxidant power is more strongly associated with fruit and vegetable intake than the individual components

BACKGROUND: Monitoring of fruit and vegetable (F&V) intake is fraught with difficulties. Available dietary assessment methods are associated with considerable error, and the use of biomarkers offers an attractive alternative. Few studies to date have examined the use of plasma biomarkers to monitor or predict the F&V intake of volunteers consuming a wide range of intakes from both habitual F&V and manipulated diets. OBJECTIVE: This study tested the hypothesis that an integrated biomarker calculated from a combination of plasma vitamin C, cholesterol-adjusted carotenoid concentration and Ferric Reducing Antioxidant Power (FRAP) had more power to predict F&V intake than each individual biomarker. METHODS: Data from a randomized controlled dietary intervention study [FLAVURS (Flavonoids University of Reading Study); n = 154] in which the test groups observed sequential increases of 2.3, 3.2, and 4.2 portions of F&Vs every 6 wk across an 18-wk period were used in this study. RESULTS: An integrated plasma biomarker was devised that included plasma vitamin C, total cholesterol-adjusted carotenoids, and FRAP values, which better correlated with F&V intake (r = 0.47, P < 0.001) than the individual biomarkers (r = 0.33, P < 0.01; r = 0.37, P < 0.001; and r = 0.14, respectively; P = 0.099). Inclusion of urinary potassium concentration did not significantly improve the correlation. The integrated plasma biomarker predicted F&V intake more accurately than did plasma total cholesterol-adjusted carotenoid concentration, with the difference being significant at visit 2 (P < 0.001) and with a tendency to be significant at visit 1 (P = 0.07). CONCLUSION: Either plasma total cholesterol-adjusted carotenoid concentration or the integrated biomarker could be used to distinguish between high- and moderate-F&V consumers. This trial was registered at www.controlled-trials.com as ISRCTN47748735.

Reduced maximal oxygen consumption and overproduction of proinflammatory cytokines in athletes

Objective: It was the aim of this study to evaluate whether chronic pain in athletes is related to performance, measured by the maximum oxygen consumption and production of hormones and cytokines. Methods: Fifty-five athletes with a mean age of 31.9 +/- 4.2 years engaged in regular competition and showing no symptoms of acute inflammation, particularly fever, were studied. They were divided into 2 subgroups according to the occurrence of pain. Plasma concentrations of adrenaline, noradrenaline, cortisol, prolactin, growth hormone and dopamine were measured by radioimmunoassay, and the production of the cytokines interleukin (IL)-1, IL-2, IL-4, IL-6, tumor necrosis factor-alpha, interferon-alpha and prostaglandin E-2 by whole-blood culture. Maximal oxygen consumption was determined during an incremental treadmill test. Results: There was no change in the concentration of stress hormones, but the athletes with chronic pain showed a reduction in maximum oxygen consumption (22%) and total consumption at the anaerobic threshold (25%), as well as increased cytokine production. Increases of 2.7-, 8.1-, 1.7- and 3.7-fold were observed for IL-1, IL-2, tumor necrosis factor-alpha and interferon-alpha, respectively. Conclusions: Our data show that athletes with chronic pain have enhanced production of proinflammatory cytokines and lipid mediators and reduced performance in the ergospirometric test. Copyright (c) 2008 S. Karger AG, Basel.