Effects of dietary fat modification on skeletal muscle fatty acid handling in the metabolic syndrome

Objective: In the metabolic syndrome (MetS), increased fat storage in ‘nonadipose’ tissues such as skeletal muscle may be related to insulin resistance (‘lipid overflow’ hypothesis). The objective of this study was to examine the effects of dietary fat modification on the capacity of skeletal muscle to handle dietary and endogenous fatty acids (FAs). Subjects and Methods: In total, 29 men with the MetS were randomly assigned to one of four diets for 12 weeks: a high-fat saturated fat diet (HSFA, n=6), a high-fat monounsaturated fat diet (HMUFA, n=7) and two low-fat high-complex carbohydrate diets supplemented with (LFHCCn−3, n=8) or without (LFHCC, n=8) 1.24 g per day docosahexaenoic and eicosapentaenoic acid. Fasting and postprandial skeletal muscle FA handling was examined by measuring arteriovenous concentration differences across the forearm muscle. [2H2]-palmitate was infused intravenously to label endogenous triacylglycerol (TAG) and free fatty acids in the circulation and subjects received a high-fat mixed meal (2.6 MJ, 61 energy% fat) containing [U-13C]-palmitate to label chylomicron-TAG. Results: Postprandial circulating TAG concentrations were significantly lower after dietary intervention in the LFHCCn−3 group compared to the HSFA group (ΔiAUC −139±67 vs 167±70 μmol l−1 min−1, P=0.009), together with decreased concentrations of [U-13C]-labeled TAG, representing dietary FA. Fasting TAG clearance across forearm muscle was decreased on the HSFA diet, whereas no differences were observed in postprandial forearm muscle FA handling between diets. Conclusion: Chronic manipulation of dietary fat quantity and quality did not affect forearm muscle FA handling in men with the MetS. Postprandial TAG concentrations decreased on the LFHCCn−3 diet, which could be (partly) explained by lower concentration of dietary FA in the circulation.

Effects of dietary fat modification on oxidative stress and inflammatory markers in the LIPGENE study.

Subjects with the metabolic syndrome (MetS) have enhanced oxidative stress and inflammation. Dietary fat quality has been proposed to be implicated in these conditions. We investigated the impact of four diets distinct in fat quantity and quality on 8-iso-PGF2α (a major F2-isoprostane and oxidative stress indicator), 15-keto-13,14-dihydro-PGF2α (15-keto-dihydro-PGF2α, a major PGF2α metabolite and marker of cyclooxygenase-mediated inflammation) and C-reactive protein (CRP). In a 12-week parallel multicentre dietary intervention study (LIPGENE), 417 volunteers with the MetS were randomly assigned to one of the four diets: two high-fat diets (38 % energy (%E)) rich in SFA or MUFA and two low-fat high-complex carbohydrate diets (28 %E) with (LFHCC n-3) or without (LFHCC) 1·24 g/d of very long chain n-3 fatty acid supplementation. Urinary levels of 8-iso-PGF2α and 15-keto-dihydro-PGF2α were determined by RIA and adjusted for urinary creatinine levels. Serum concentration of CRP was measured by ELISA. Neither concentrations of 8-iso-PGF2α and 15-keto-dihydro-PGF2α nor those of CRP differed between diet groups at baseline (P>0·07) or at the end of the study (P>0·44). Also, no differences in changes of the markers were observed between the diet groups (8-iso-PGF2α, P = 0·83; 15-keto-dihydro-PGF2α, P = 0·45; and CRP, P = 0·97). In conclusion, a 12-week dietary fat modification did not affect the investigated markers of oxidative stress and inflammation among subjects with the MetS in the LIPGENE study.

Dietary fat modifications and blood pressure in subjects with the metabolic syndrome in the LIPGENE dietary intervention study

Hypertension is a key feature of the metabolic syndrome. Lifestyle and dietary changes may affect blood pressure (BP), but the knowledge of the effects of dietary fat modification in subjects with the metabolic syndrome is limited. The objective of the present study was to investigate the effect of an isoenergetic change in the quantity and quality of dietary fat on BP in subjects with the metabolic syndrome. In a 12-week European multi-centre, parallel, randomised controlled dietary intervention trial (LIPGENE), 486 subjects were assigned to one of the four diets distinct in fat quantity and quality: two high-fat diets rich in saturated fat or monounsaturated fat and two low-fat, high-complex carbohydrate diets with or without 1·2 g/d of very long-chain n-3 PUFA supplementation. There were no overall differences in systolic BP (SBP), diastolic BP or pulse pressure (PP) between the dietary groups after the intervention. The high-fat diet rich in saturated fat had minor unfavourable effects on SBP and PP in males.

Milk and meat in our diet: good or bad for health?

Foods derived from animals are an important source of nutrients in the diet but there is considerable uncertainty about whether or not these foods contribute to increased risk of various chronic diseases. For milk in particular there appears to be an enormous mismatch between both the advice given on milk/dairy foods items by various authorities and public perceptions of harm from the consumption of milk and dairy products, and the evidence from long-term prospective cohort studies. Such studies provide convincing evidence that increased consumption of milk can lead to reductions in the risk of vascular disease and possibly some cancers and of an overall survival advantage from the consumption of milk, although the relative effect of milk products is unclear. Accordingly, simply reducing milk consumption in order to reduce saturated fatty acid (SFA) intake is not likely to produce benefits overall though the production of dairy products with reduced SFA contents is likely to be helpful. For red meat there is no evidence of increased risk of vascular diseases though processed meat appears to increase the risk substantially. There is still conflicting and inconsistent evidence on the relationship between consumption of red meat and the development of colorectal cancer, but this topic should not be ignored. Likewise, the role of poultry meat and its products as sources of dietary fat and fatty acids is not fully clear. There is concern about the likely increase in the prevalence of dementia but there are few data on the possible benefits or risks from milk and meat consumption. The future role of animal nutrition in creating foods closer to the optimum composition for long-term human health will be increasingly important. Overall, the case for increased milk consumption seems convincing, although the case for high-fat dairy products and red meat is not. Processed meat products do seem to have negative effects on long-term health and although more research is required, these effects do need to be put into the context of other risk factors to long-term health such as obesity, smoking and alcohol consumption.

Effect of feed restriction and supplemental dietary fat on gut peptide and hypothalamic neuropeptide mRNA concentrations in growing wethers

The objectives of the present study were 1) to evaluate the effects of supplemental fat and ME intake on plasma concentrations of glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK), glucose-dependent insulinotropic polypeptide, ghrelin, and oxyntomodulin; and 2) to determine the association of these peptides with DMI and the hypothalamic concentration of mRNA for the following neuropeptides: neuropeptide Y (NPY), agouti-related peptide (AgRP), and proopiomelanocortin (POMC). In a completely randomized block design with a 2 x 2 factorial arrangement of treatments, 32 pens with 2 wethers each were restricted-fed (2.45 Mcal/lamb per day) or offered diets ad libitum (n = 16) with or without 6% supplemental fat (n = 16) for a period of 30 d. Dry matter intake was measured daily. On d 8, 15, 22, and 29, BW was measured before feeding, and 6 h after feeding, blood samples were collected for plasma measurement of insulin, GLP-1, CCK, ghrelin, glucose-dependent insulinotropic polypeptide, oxyntomodulin, glucose, and NEFA concentrations. On d 29, blood was collected 30 min before feeding for the same hormone and metabolite analyses. At the end of the experiment, wethers were slaughtered and the hypothalami were collected to measure concentrations of NPY, AgRP, and POMC mRNA. Offering feed ad libitum (resulting in greater ME intake) increased plasma insulin and NEFA concentrations (P = 0.02 and 0.02, respectively) and decreased hypothalamic mRNA expression of NPY and AgRP (P = 0.07 and 0.02, respectively) compared with the restricted-fed wethers. There was a trend for the addition of dietary fat to decrease DMI (P = 0.12). Addition of dietary fat decreased insulin and glucose concentrations (P < 0.05 and 0.01, respectively) and tended to increase hypothalamic mRNA concentrations for NPY and AgRP (P = 0.07 and 0.11, respectively). Plasma GLP-1 and CCK concentrations increased in wethers offered feed ad libitum compared with restricted-fed wethers, but the response was greater when wethers were offered feed ad libitum and had supplemental fat in the diet (fat x intake interaction, P = 0.04). The prefeeding plasma ghrelin concentration was greater in restricted-fed wethers compared with those offered feed ad libitum, but the concentrations were similar 6 h after feeding (intake x time interaction, P < 0.01). Supplemental dietary fat did not affect (P = 0.22) plasma ghrelin concentration. We conclude that insulin, ghrelin, CCK, and GLP-1 may regulate DMI in sheep by regulating the hypothalamic gene expression of NPY, AgRP, and POMC.

Improving the efficiency of energy utilization in cattle

The efficiency of energy utilisation in cattle is a determinant of the profitability of milk and beef production, as well as their environmental impact. At an animal level, meat and milk production by ruminants is less efficient than pig and poultry production, in part due to lower digestibility of forages compared with grains. However, when compared on the basis of human-edible inputs, the ruminant has a clear efficiency advantage. There has been recent interest in feed conversion efficiency (FCE) in dairy cattle and residual feed intake, an indicator of FCE, in beef cattle. Variation between animals in FCE may have genetic components, allowing selection for animals with greater efficiency and reduced environmental impact. A major source of variation in FCE is feed digestibility, and thus approaches that improve digestibility should improve FCE if rumen function is not disrupted. Methane represents a substantial loss of digestible energy from rations. Major determinants of methane emission are the amount of feed consumed and the proportions of forage and concentrates fed. In addition, feeding fat has long been known to reduce methane emission. A myriad of other supplements and additives are currently being investigated as mitigators of methane emission, but in many cases compounds effective in sheep are ineffective in lactating dairy cows. Ultimately, the adoption of ‘best practice’ in diet formulation and management may be the most effective option for reducing methane. In assessing the efficiency of energy use for milk and meat production by cattle, and their environmental impact, it is imperative that comparisons be made at a systems level, and that the wider social and economic implications of mitigation policy are considered.

Effect of feeding fat or intrajugular infusion of glucagon-like peptide-1 and cholecystokinin on dry matter intake, digestibility, and digesta rate of passage in growing wethers

A cause and effect relationship between glucagon-like peptide 1 (7, 36) amide (GLP-1) and cholecystokinin (CCK) and DMI regulation has not been established in ruminants. Three randomized complete block experiments were conducted to determine the effect of feeding fat or infusing GLP-1 or CCK intravenously on DMI, nutrient digestibility, and Cr rate of passage (using Cr(2)O(3) as a marker) in wethers. A total of 18 Targhee × Hampshire wethers (36.5 ± 2.5 kg of BW) were used, and each experiment consisted of four 21-d periods (14 d for adaptation and 7 d for infusion and sampling). Wethers allotted to the control treatments served as the controls for all 3 experiments; experiments were performed simultaneously. The basal diet was 60% concentrate and 40% forage. In Exp. 1, treatments were the control (0% added fat) and addition of 4 or 6% Ca salts of palm oil fatty acids (DM basis). Treatments in Exp. 2 and 3 were the control and 3 jugular vein infusion dosages of GLP-1 (0.052, 0.103, or 0.155 µg•kg of BW(-1)•d(-1)) or CCK (0.069, 0.138, or 0.207 µg•kg of BW(-1)•d(-1)), respectively. Increases in plasma GLP-1 and CCK concentrations during hormone infusions were comparable with increases observed when increasing amounts of fat were fed. Feeding fat and infusion of GLP-1 tended (linear, P = 0.12; quadratic, P = 0.13) to decrease DMI. Infusion of CCK did not affect (P > 0.21) DMI. Retention time of Cr in the total gastrointestinal tract decreased (linear, P < 0.01) when fat was fed, but was not affected by GLP-1 or CCK infusion. In conclusion, jugular vein infusion produced similar plasma CCK and GLP-1 concentrations as observed when fat was fed. The effects of feeding fat on DMI may be partially regulated by plasma concentration of GLP-1, but are not likely due solely to changes in a single hormone concentration.

Redox-active polymers based on nonbridged metal−metal bonds. Electrochemical formation of [Os(bpy)(CO)(L)]n(bpy = 2,2‘-bipyridine; L = CO, MeCN) and of their reduced forms: a spectroelectrochemical study

IR, UV-vis, and EPR spectroelectrochemistry at variable temperatures and in different solvents were applied to investigate in situ the formation of electroactive molecular chains with a nonbridged Os-Os backbone, in particular, the polymer [Os-0(bpy)(CO)(2)](n), (bpy = 2,2'-bipyridine), from a mononuclear Os(II) carbonyl precursor, [Os-II(bpy)(CO)(2)Cl-2]. The one-electron-reduced form, [Os-II(bpy(.-))(CO)(2)Cl-2](-), has been characterized spectroscopically at low temperatures. This radical anion is the key intermediate in the electrochemical propagation process responsible for the metal-metal bond formation. Unambiguous spectroscopic evidence has been gained also for the formation of [{Os-0(bpy(.-))(CO)(2)}(-)](n), the electron-rich electrocatalyst of CO2 reduction. The polymer species are fairly well soluble in butyronitrile, which is important for their potential utilization in nanoscience, for example, as conducting molecular wires. We have also shown that complete solubility is accomplished for the monocarbonyl-acetonitrile derivative of the polymer, [Os-0(bpy)(CO)(MeCN)(2)Cl](n).

Reduced-order modelling of a high-voltage oscillatory impulse generator

The design of high-voltage equipment encompasses the study of oscillatory surges caused by transients such as those produced by switching. By obtaining a model, the response of which reconstructs that observed in the actual system, simulation studies and critical tests can be carried out on the model rather than on the equipment itself. In this paper, methods for the construction of simplified models are described and it is shown how the use of a complex model does not necessarily result in superior response pattern reconstruction.

Use of Megasphaera elsdenii NCIMB41125 as a probiotic for early-lactation dairy cows: effects on rumen pH and fermentation patterns

Multiparous rumen-fistulated Holstein cows were fed, from d 1 to 28 post-calving, an ad libitum TMR containing (g/kg DM) grass silage (196), corn silage (196), wheat (277), soybean meal (100), and other feeds (231) with CP, NDF, starch and water soluble carbohydrate concentrations of 176, 260, 299 and 39 g/kg DM respectively and ME of 12.2 MJ/kg DM. Treatments consisting of a minimum of 1010 cfu Megasphaera elsdenii NCIMB 41125 in 250 ml solution (MEGA) or 250 ml of autoclaved M. elsdenii (CONT) were administered via the rumen cannula on d 3 and 12 of lactation (n=7 per treatment). Mid-rumen pH was measured every 15 minutes and eating and ruminating behavior was recorded for 24 h on d 2, 4, 6, 8, 11, 13, 15, 17, 22 and 28. Rumen fluid for VFA and lactic acid (LA) analysis was collected at 11 timepoints on each of d 2, 4, 6, 13 and 15. Data were analysed as repeated measures using the Glimmix (LA data) or Mixed (all other data) procedures of SAS with previous 305 d milk yield and d 2 measurements as covariates where appropriate. Milk yield was higher (CONT 43.0 vs MEGA 45.4 ±0.75 kg/d, P=0.051) and fat concentration was lower (CONT 45.6 vs MEGA 40.4 ±1.05 g/kg, P=0.005) in cows that received MEGA. Time spent eating (263 ±15 min/d) and ruminating (571 ±13 min/d), DM intake (18.4 ±0.74 kg/d), proportion of each 24 h period with rumen pH below 5.6 (3.69 ±0.94 h) and LA concentrations (2.00 mM) were similar (P>0.327) across treatments. Ruminal total VFA concentration (104 ±3 mM) was similar (P=0.404) across treatments, but a shift from acetate (CONT 551 vs MEGA 524 ±14 mmol/mol VFA, P=0.161) to propionate production (CONT 249 vs MEGA 275 ±11 mmol/mol VFA, P=0.099) meant that the acetate:propionate ratio (CONT 2.33 vs MEGA 1.94 ±0.15) was reduced (P=0.072) in cows that received MEGA. This study provides evidence that supplementation of early lactation dairy cows with MEGA alters rumen fermentation patterns in favour of propionate, with potential benefits for animal health and productivity.

A hypoplastic model of skeletal muscle development displaying reduced foetal myoblast cell numbers, increased oxidative myofibres and improved specific tension capacity

The major component of skeletal muscle is the myofibre. Genetic intervention inducing over-enlargement of myofibres beyond a certain threshold through acellular growth causes a reduction in the specific tension generating capacity of the muscle. However the physiological parameters of a genetic model that harbours reduced skeletal muscle mass have yet to be analysed. Genetic deletion of Meox2 in mice leads to reduced limb muscle size and causes some patterning defects. The loss of Meox2 is not embryonically lethal and a small percentage of animals survive to adulthood making it an excellent model with which to investigate how skeletal muscle responds to reductions in mass. In this study we have performed a detailed analysis of both late foetal and adult muscle development in the absence of Meox2. In the adult, we show that the loss of Meox2 results in smaller limb muscles that harbour reduced numbers of myofibres. However, these fibres are enlarged. These myofibres display a molecular and metabolic fibre type switch towards a more oxidative phenotype that is induced through abnormalities in foetal fibre formation. In spite of these changes, the muscle from Meox2 mutant mice is able to generate increased levels of specific tension compared to that of the wild type.