Fat from Hermetia illucens Alters the Cecal Gut Microbiome and Lowers Hepatic Triglyceride Concentration in Comparison to Palm Oil in Obese Zucker Rats.

BACKGROUND: Palm oil (PO) is the most widely utilized plant oil for food production. Owing to the great ecologic problems associated with PO production, sustainably produced fats, such as insect fat, might be a suitable alternative. OBJECTIVES: The hypothesis was tested that fat from Hermetia illucens larvae (HF) compared with PO and soybean oil (SO) has no adverse effects on hepatic lipid metabolism, plasma metabolome, and cecal microbiome in obese Zucker rats. METHODS: Thirty male obese Zucker rats were randomly assigned to 3 groups (SO, PO, HF; n = 10 rats/group) and fed 3 different semisynthetic diets containing either SO, PO, or HF as the main fat source for 4 wk. The effects were evaluated by measurement of liver and plasma lipid concentrations, liver transcriptomics, targeted plasma metabolomics, and cecal microbiomics. RESULTS: Supplementation of HF reduced hepatic triglyceride concentration and messenger ribonucleic acid concentrations of selected genes involved in fatty acid and triglyceride synthesis in comparison to PO (P < 0.05). Pairwise comparison of the Simpson index and Jaccard index showed a higher cecal microbial α- and ß-diversity in rats fed the HF diet than in rats fed the PO diet (P = 0.015 and P = 0.027), but no difference between rats fed the diets with SO or PO. Taxonomic analysis of the cecal microbial community revealed a lower abundance of Clostridium_sensu_stricto_1 and a higher abundance of Blautia, Mucispirillum, Anaerotruncus, Harryflintia, and Peptococcus in rats supplemented with HF than in rats supplemented with PO (P < 0.05). CONCLUSIONS: HF, compared with PO, has liver lipid-lowering effects in obese Zucker rats, which may be caused by a shift in the gut microbial community. Thus, HF might serve as a sustainably produced fat alternative to PO for food production.

Association of cardiorespiratory fitness level with vascular function and subclinical atherosclerosis in the elderly.

PURPOSE: Physical exercise is crucial for healthy aging and plays a decisive role in the prevention of atherosclerotic cardiovascular disease (ASCVD). A higher level of cardiorespiratory fitness (CRF) in the elderly is associated with lower cardiovascular and all-cause mortality. This study investigated the association of CRF level with vascular function and cardiovascular risk factors in the elderly. METHODS: We examined 79 apparently healthy and physically active subjects aged > 55 years (64 ± 4 years). Cardiovascular functional parameters assessed included brachial and central blood pressure (BP), pulse wave velocity (PWV), augmentation index (Aix), and ankle-brachial index. Sonography of the common carotid artery was performed. CRF level was determined by a cardiopulmonary exercise test, and everyday activity was quantified with an accelerometer. RESULTS: All participants had a higher CRF level than the reported age-specific normative values. Twenty-nine subjects had subclinical atherosclerosis of the common carotid artery. Compared with participants without atherosclerosis, they were older (p = 0.007), displayed higher brachial systolic BP (p = 0.006), and higher central systolic BP (p = 0.014). Lower brachial (p = 0.036) and central (p = 0.003) systolic BP, lower PWV (p = 0.004), lower Aix (p < 0.001), lower body fat percentage (< 0.001), and lower LDL cholesterol (p = 0.005) were associated with a higher CRF level. CONCLUSIONS: In this cohort of healthy and physically active individuals, subjects with subclinical atherosclerosis displayed higher systolic brachial and central BP. A higher CRF level was associated with enhanced vascular function, consistent with an influence of CRF on both BP and vascular function in the elderly.

Effect of dietary phosphorus deprivation during the dry period on the liver transcriptome of high-yielding periparturient dairy cows.

Although dietary phosphorus (P) deprivation extending from the dry period into early lactation impairs health and productivity of cows, restricting dietary P supply during the dry period not only appears to be innocuous but rather effectively mitigates hypocalcemia during the first wk of lactation. To investigate possible negative metabolic effects of P deprivation during the dry period, the present study tested the hypothesis that restricted dietary P supply during the dry period alters the liver transcriptome of dairy cows during the periparturient period. Thirty late-pregnant multiparous Holstein-Friesian dairy cows entering their second, third, or fourth lactation were assigned to either a dry cow ration with low (LP, 0.16% P in DM) or adequate P content (AP, 0.35% in DM) during the last 4 wk of the dry period (n = 15/group). Liver transcriptomics, which was carried out in a subset of 5 second-parity cows of each group (n = 5), and determination of selected hormones and metabolites in blood of all cows, was performed ∼1 wk before calving and on d 3 postpartum. Liver tissue specimens and blood samples were obtained by a micro-invasive biopsy technique from the right tenth intercostal space and puncture of a jugular vein, respectively. One hundred seventy-five hepatic transcripts were expressed differentially between LP versus AP cows in late pregnancy, and 165 transcripts differed between LP versus AP cows in early lactation (fold change >1.3 and <-1.3, P < 0.05). In late pregnancy, the enriched biological processes of the upregulated and the downregulated transcripts were mainly related to immune processes and signal transduction (P < 0.05), respectively. In early lactation, the enriched biological processes of the upregulated and the downregulated transcripts were involved in mineral transport and biotransformation (P < 0.05), respectively. The plasma concentrations of the hormones and acute-phase proteins (progesterone, insulin-like growth factor 1, serum amyloid α, haptoglobin, and 17ß-estradiol) determined were not affected by P supply. These results suggest that P deprivation during the dry period moderately affects the liver transcriptome of cows in late pregnancy and early lactation, and causes no effects on important plasma hormones and acute-phase proteins indicating no obvious impairment of health or metabolism of the cows.

Effect of supplementation of vitamin D3 or vitamin D2 on serum concentrations of free and total 25-hydroxyvitamin D and the expression of genes involved in immune function in peripheral blood mononuclear cells of weaned pigs.

The present study aimed to compare the effects of vitamin D2 and vitamin D3 supplementation on concentrations of total and free 25(OH)D in plasma and the expression of genes involved in the innate immune system in peripheral blood mononuclear cells (PBMC) in weaned pigs. Five groups of pigs (with an initial body weight of around 9 kg) received basal diets supplemented with either 500 (control group), 1000 or 2000 IU vitamin D3/kg diet or 1000 or 2000 IU vitamin D2/kg diet for a period of 4 weeks. Vitamin D supplementation did not influence feed intake, body weight gain, feed conversion ratio, apparent total tract digestibility of calcium and phosphorus, and serum concentrations of calcium, inorganic phosphate and parathyroid hormone. Supplementation of vitamin D3 led to a dose-dependent increase of the concentrations of total and free 25(OH)D in serum. In contrast, pigs supplemented with 1000 or 2000 IU vitamin D2/kg diet did not have higher concentrations of total and free 25(OH)D in serum than the control group. The ratio of free/total 25(OH)D in serum was not influenced by vitamin D3 supplementation, whereas the group supplemented with 2000 IU vitamin D2/kg diet had a higher free/total 25(OH)D ratio than the groups supplemented with 1000 or 2000 IU vitamin D3/kg diet. Genes involved in vitamin D signalling (CYP27B1, VDR), as well as pro-inflammatory and immune regulatory genes (TLR4, TNF, IL1B and TGFB1) and genes encoding porcine protegrins (NPG1, NPG4), proteins belonging to the group of antimicrobial peptides, in PBMC were not different among groups supplemented with vitamin D3 or vitamin D2 and the control group. Therefore, the study indicates that supplementation of vitamin D2 causes much lower levels of total 25(OH)D than supplementation of vitamin D3 and that supplementation of vitamins D2 or D3 at moderate levels does not have an impact on the innate immune function in healthy pigs.

Replacement of soybean oil by Hermetia illucens larvae fat in broiler diets alters the breast muscle lipidome and reduces lipid oxidation of the breast muscle during heat-processing.

Replacement of soybean oil by insect fat from Hermetia illucens (HI) has been reported to increase the proportions of saturated fatty acids (SFA) and decrease those of polyunsaturated fatty acids (PUFA) in total lipids of breast and thigh meat in broilers. Since the susceptibility of meat to oxidation is strongly dependent on its PUFA content, the present study hypothesised that replacement of soybean oil by HI larvae fat in broiler diets reduces the formation of lipid oxidation products, including oxidation products of cholesterol and phytosterols, in heat-processed breast muscle of broilers. To test this hypothesis, 100 male, 1-day-old Cobb 500 broilers were assigned to three groups and fed three different nutrient adequate diets, which varied only in the fat source (group HI-0: 0% HI larvae fat and 5% soybean oil; group HI-2.5: 2.5% HI larvae fat and 2.5% soybean oil; group HI-5.0: 5.0% HI larvae fat and 0% soybean oil), in a three-phase feeding system for 35 days. While the growth performance of the broilers was not different, the absolute and relative breast muscle weights were higher in group HI-5.0 than in group HI-0 (p < 0.05). The proportions of C12:0, C14:0, C14:1, C16:0, C16:1 and total SFA were higher and those of C18:1, C18:2 n-6, C18:3 n-3 and total PUFA were lower in breast muscle total lipids of group HI-5.0 than in groups HI-2.5 and HI-0 (p < 0.05). Lipidomic analysis of breast muscle revealed that the concentration of triacylglycerols was 46% and 53% lower in groups HI-2.5 and HI-5.0, respectively, than in group HI-0 (p < 0.05), whereas all other lipid classes detected did not differ among groups. Concentrations of thiobarbituric acid-reactive substances, 7α-hydroxycholesterol, 7ß-hydroxycholesterol and total cholesterol oxidation products in heat-processed breast muscle were lower in group HI-5.0 than in group HI-0 (p < 0.05). Concentrations of oxidation products of phytosterols in heat-processed breast muscle were generally much lower than those of cholesterol oxidation products and did not differ between the three groups of broilers. In conclusion, complete replacement of soybean oil with HI larvae fat in broiler diets strongly alters the fatty acid composition of breast muscle total lipids and reduce lipid oxidation of the breast muscle during heat-processing.

Inflammation and necrosis syndrome is associated with alterations in blood and metabolism in pigs.

BACKGROUND: Swine inflammation and necrosis syndrome (SINS) can lead to significant clinical alterations at tail, ears, claws and other parts of the body in suckling piglets, weaners and fatteners. Clinical findings are associated with vasculitis, intima proliferation and thrombosis. The syndrome can be found in newborns, indicating a primarily endogenous aetiology. It has been hypothesized that SINS is triggered by gut-derived microbial-associated molecular patterns, causing derangements in liver metabolism and activity of peripheral white blood cells involving inflammation and blood haemostasis. In order to characterize these metabolic derangements of SINS for the first time, red and white blood counts, parameters of blood haemostasis, serum metabolites and acute phase proteins in the serum were analysed in 360 piglets, weaners and fatteners, each with significantly different SINS scores. RESULTS: SINS scores and haematological/clinical chemical parameters were significantly associated (P < 0.05), especially in weaners and fatteners. Higher degrees of clinical SINS were associated with increased numbers of monocytes and neutrophils. Blood coagulation was altered in weaners and a thrombocytopenia was found in fatteners. Additionally, acute phase proteins, especially C-reactive protein and fibrinogen were increased in serum. Serum metabolites and serum liver enzymes were slightly altered. Aspartate transaminase levels overall exceeded physiological limit and increased in parallel with SINS scores in fatteners. CONCLUSION: Clinical inflammation and necrosis at tail, ears, claws and other parts of the body were significantly associated with haematology and serum clinical chemistry, especially in weaners and fatteners. The involvement of inflammatory cells, blood coagulation, acute phase proteins and certain serum metabolites support the inflammatory-necrotising character of the syndrome and provide starting points for further studies to decipher its exact pathogenesis. The low to moderate variations seem less suitable for diagnostic use.

Vitamin D in dairy cows: metabolism, status and functions in the immune system.

The function of vitamin D in calcium homoeostasis in dairy cows, such as in other vertebrates, is known for many years. In recent years, new and interesting, non-classical functions of vitamin D have been elucidated, including effects on the immune system. The major aim of this review is to provide an overview of effects of vitamin D or its metabolites on the immune system in dairy cows. The first part of the review provides an overview of vitamin D metabolism, with particular reference to the role of various proteins (25- and 1-hydroxylases, vitamin D binding protein, vitamin D receptor) in vitamin D signalling. The second part deals with the role of the concentration of 25-hydroxyvitamin D [25(OH)D] in plasma as an indicator of the vitamin D status in dairy cows, and its dependence on sunlight exposure and dietary vitamin D supplementation. In this part also the "free hormone hypothesis" is discussed, indicating that the concentration of free 25(OH)D might be a more valid indicator of the vitamin D status than the concentration of total 25(OH)D. The third part deals with classical and the non-classical functions of vitamin D. Among the non-classical functions which are based on an autocrine vitamin D signalling, particular reference is given to the effects of vitamin D and vitamin D metabolites on the immune system in bovine immune cells and in dairy cows. Recent findings provide some indication that vitamin D or its metabolite 25(OH)D could enhance the immune function in dairy cows and be useful for the prevention and therapy of mastitis. However, the number of studies reported so far in this respect is very limited. Thus, much more research is required to yield clear concepts for an optimised usage of vitamin D to improve the immune system and prevent infectious diseases in dairy cows.

Resveratrol Alleviates the Inhibitory Effect of Tunicamycin-Induced Endoplasmic Reticulum Stress on Expression of Genes Involved in Thyroid Hormone Synthesis in FRTL-5 Thyrocytes.

Recently, ER stress induced by tunicamycin (TM) was reported to inhibit the expression of key genes involved in thyroid hormone synthesis, such as sodium/iodide symporter (NIS), thyroid peroxidase (TPO) and thyroglobulin (TG), and their regulators such as thyrotropin receptor (TSHR), thyroid transcription factor-1 (TTF-1), thyroid transcription factor-2 (TTF-2) and paired box gene 8 (PAX-8), in FRTL-5 thyrocytes. The present study tested the hypothesis that resveratrol (RSV) alleviates this effect of TM in FRTL-5 cells. While treatment of FRTL-5 cells with TM alone (0.1 µg/mL) for 48 h strongly induced the ER stress-sensitive genes heat shock protein family A member 5 (HSPA5) and DNA damage inducible transcript 3 (DDIT3) and repressed NIS, TPO, TG, TSHR, TTF-1, TTF-2 and PAX-8, combined treatment with TM (0.1 µg/mL) and RSV (10 µM) for 48 h attenuated this effect of TM. In conclusion, RSV alleviates TM-induced ER stress and attenuates the strong impairment of expression of genes involved in thyroid hormone synthesis and their regulators in FRTL-5 thyrocytes exposed to TM-induced ER stress. Thus, RSV may be useful for the treatment of specific thyroid disorders, provided that strategies with improved oral bioavailability of RSV are applied.

Effect of Ecdysterone on the Hepatic Transcriptome and Lipid Metabolism in Lean and Obese Zucker Rats.

Conflicting reports exist with regard to the effect of ecdysterone, the predominating representative of steroid hormones in insects and plants, on hepatic and plasma lipid concentrations in different rodent models of obesity, fatty liver, and diabetes, indicating that the effect is dependent on the rodent model used. Here, the hypothesis was tested for the first time that ecdysterone causes lipid-lowering effects in genetically obese Zucker rats. To test this hypothesis, two groups of male obese Zucker rats (n = 8) were fed a nutrient-adequate diet supplemented without or with 0.5 g ecdysterone per kg diet. To study further if ecdysterone is capable of alleviating the strong lipid-synthetic activity in the liver of obese Zucker rats, the study included also two groups of male lean Zucker rats (n = 8) which also received either the ecdysterone-supplemented or the non-supplemented diet. While hepatic and plasma concentrations of triglycerides and cholesterol were markedly higher in the obese compared to the lean rats (p < 0.05), hepatic and plasma triglyceride and cholesterol concentrations did not differ between rats of the same genotype fed the diets without or with ecdysterone. In conclusion, the present study clearly shows that ecdysterone supplementation does not exhibit lipid-lowering actions in the liver and plasma of lean and obese Zucker rats.

Effect of Tenebrio molitor larvae meal on the antioxidant status and stress response pathways in tissues of growing pigs.

Insect meal (IM) produced from edible insects, such as Tenebrio molitor, has been recognised as a potentially suitable protein component in feeding rations for monogastric livestock. While several studies with broilers have shown that animal´s health is not negatively affected by IM, less is known with regard to the influence of IM on metabolism of pigs. The present study investigates whether IM from Tenebrio molitor larvae causes oxidative stress and activates oxidative stress-sensitive signalling pathways in key metabolic tissues of pigs. To address this question, male 5-week-old crossbred pigs were randomly assigned to three groups of 10 pigs each and fed nutrient-adequate, isonitrogenous diets either without (CON) or with 5% IM or 10% IM from Tenebrio molitor larvae for 4 weeks. Concentrations of thiobarbituric acid reactive substances, tocopherols and glutathione in liver, gastrocnemius muscle and/or plasma did not differ between groups. Activities of the antioxidant enzymes catalase (CAT), glutathione peroxidase (GPX) and superoxide dismutase (SOD) in the liver and of GPX and SOD in gastrocnemius muscle were not different between groups, whereas the activity of CAT in skeletal muscle was increased in the two IM-fed groups compared to group CON (p < 0.05). The mRNA levels of most of the target genes of oxidative stress-sensitive signalling pathways, such as nuclear factor-κB, nuclear factor erythroid 2-related factor 2 and endoplasmic reticulum stress-induced unfolded protein response, in liver and gastrocnemius muscle did not differ between the three groups. The present study shows that feeding a diet containing adequate levels of antioxidants, such as vitamin E and selenium, and Tenebrio molitor larvae meal as a protein component neither causes oxidative stress nor activates oxidative stress-sensitive signalling pathways in key metabolic tissues of growing pigs. Based on these observations, IM from Tenebrio molitor larvae can be regarded as a safe source of protein in growing pigs.

Combined effects of moderate exercise and short-term fasting on markers of immune function in healthy human subjects.

This study aimed to investigate the effects of a short-term (36 h) fasting period combined with an acute bout of exercise on markers of immune function and inflammation in healthy human subjects. Fourteen moderately trained male subjects (aged 19-39 yr) participated in a 36-h fasting trial (FA-T), followed by an acute bout of moderate exercise (60% V̇o2max). After 1 wk, the same subjects, as their own control, participated in a nonfasting trial (NFA-T) in which they performed an exercise trial of the same duration and intensity. Blood samples were taken before, immediately after, and 1 h after each exercise bout and analyzed for several immunological and metabolic markers. At baseline, fasting subjects showed lower levels of T cell apoptosis, lymphocyte-proliferative responses, IL-6, monocyte chemoattractant protein-1 (MCP-1), insulin, and leptin (P < 0.05) as well as higher levels of neutrophil oxidative burst and thiobarbituric acid reactive substances (TBARS) than those in the NFA-T (P < 0.05). After the exercise protocol, fasted subjects revealed higher T cell apoptosis, neutrophil oxidative burst, TBARS, TNFα, and MCP-1 levels as well as lower levels of lymphocyte-proliferative response, IL-6, insulin, and leptin than those in the NFA-T (P < 0.05). Short-term fasting aggravates perturbations in markers of immune function, and inflammation was induced by an acute moderate-intensity exercise protocol.

Insect Meal as Alternative Protein Source Exerts Pronounced Lipid-Lowering Effects in Hyperlipidemic Obese Zucker Rats.

BACKGROUND: Specific dietary proteins exert strong health-related effects compared with casein. OBJECTIVE: Herein, the hypothesis was tested using screening and conventional biochemical and molecular biological techniques that protein-rich insect meal compared with casein influences metabolic health in hyperlipidemic rats. METHODS: A 4-wk feeding trial with male, 8-wk-old homozygous obese Zucker rats (n = 36) and male, 8-wk-old heterozygous lean Zucker rats (n = 12) was performed. Obese rats were randomly divided into 3 obese groups (OC, OI50, and OI100) of 12 rats each and lean rats served as a lean control group (LC). LC and OC were fed a control diet with 20% casein as protein source, whereas in OI50 and OI100 50% and 100% of the casein, respectively, was replaced isonitrogenously by insect meal from Tenebrio molitor L. All data were analyzed by 1-factor ANOVA, except transcriptomic data which were analyzed by groupwise comparisons with the OC group. RESULTS: Transcript profiling revealed a coordinated inhibition by -17% to -521% and -37% to -859% of genes involved in fatty acid, triacylglycerol (TG), and cholesterol biosynthesis in the livers of OI100 and OI50, respectively, compared with OC (P < 0.05). Enzyme activities of fatty acid synthase, glucose-6 phosphate dehydrogenase, and 3-hydroxy-3-methylglutaryl-coenzyme-A reductase in the liver were 100-150% greater in OC compared with LC, but reduced by 50-60% in OI100 compared with OC (P < 0.05), to the same level as in LC. Liver and plasma concentrations of TG and cholesterol were 250-1000%, 30-800%, and 40-600% higher in OC, OI50, and OI100, respectively, than in LC (P < 0.05), but 40-60% and 20-60% lower in OI100 and OI50, respectively, than in group OC (P < 0.05). Plasma and liver concentrations of homocysteine were 20-30% lower in group OI100 than in group OC (P < 0.05). CONCLUSION: Insect meal exerts pronounced lipid-lowering effects in hyperlipidemic rats and, thus, might be useful for hyperlipidemic individuals.

Effect of lifelong carnitine supplementation on plasma and tissue carnitine status, hepatic lipid metabolism and stress signalling pathways and skeletal muscle transcriptome in mice at advanced age.

While strong evidence from clinical studies suggests beneficial effects of carnitine supplementation on metabolic health, serious safety concerns associated with carnitine supplementation have been raised from studies in mice. Considering that the carnitine doses in these mice studies were up to 100 times higher than those used in clinical studies, the present study aimed to address possible safety concerns associated with long-term supplementation of a carnitine dose used in clinical trials. Two groups of NMRI mice were fed either a control or a carnitine-supplemented diet (1 g/kg diet) from weaning to 19 months of age, and parameters of hepatic lipid metabolism and stress signalling and skeletal muscle gene expression were analysed in the mice at 19 months of age. Concentrations of free carnitine and acetylcarnitine in plasma and tissues were higher in the carnitine than in the control group (P<0·05). Plasma concentrations of free carnitine and acetylcarnitine were higher in mice at adult age (10 and 15 months) than at advanced age (19 months) (P<0·05). Hepatic mRNA and protein levels of genes involved in lipid metabolism and stress signalling and hepatic and plasma lipid concentrations did not differ between the carnitine and the control group. Skeletal muscle transcriptome analysis in 19-month-old mice revealed only a moderate regulation between carnitine and control group. Lifelong carnitine supplementation prevents an age-dependent impairment of plasma carnitine status, but safety concerns associated with long-term supplementation of carnitine at doses used in clinical trials can be considered as unfounded.

Effects of L-methionine on performance, gut morphology and antioxidant status in gut and liver of piglets in relation to DL-methionine.

This study investigated the hypothesis that dietary supplementation of L-methionine (L-Met) in weaned piglets in relation to DL-methionine (DL-Met) results in a higher antioxidant status and lower need for antioxidant enzyme activation in intestinal epithelium and body tissues, and improves gut morphology and gut barrier function as well as performance. A total of 99 early-weaned 21-day old piglets were allotted to six groups and fed a semi-synthetic wheat-barley-based basal diet supplemented with 0.067%, 0.107% and 0.147% of either DL-Met (MetAmino; Evonik, Hanau, Germany) or L-Met (L-Met100; CJ Europe, Schwalbach am Taunus, Germany) to reach dietary Met concentrations of 0.16%, 0.20% and 0.24%, of which the latter met the requirements for maintenance and growth based on a pre-experiment. Feed intake and body weights were recorded weekly, and samples of plasma, liver and duodenum and jejunum mucosa were collected after 3 weeks at slaughter. Plasma concentrations of L-Met were similar, and those of D-Met and total Met were higher in piglets fed DL-Met in relation to those fed L-Met. Feed intake, daily gains and feed:gain ratio, and the relative bio-efficacy based on gains and feed:gain ratio were similar for both groups. Likewise, villi length, crypt depth, the villi length:crypt depth ratio in duodenum and jejunum and gene expression of tight junction proteins in the jejunum did not differ. Concentrations of antioxidants like glutathione and tocopherol, the total antioxidant capacity, the mRNA abundance or activity of antioxidant enzymes like superoxide dismutase and glutathione peroxidase, concentrations of thiobarbituric acid reactive substances, markers for oxidative damage of lipids and the expression of inflammatory genes were similar in liver and jejunum mucosa. These data indicate that the effects of L-Met and DL-Met supplementation are comparable considering both piglet performance and parameters of gut health and function like gut morphology and the intestinal antioxidant status.

Effects of leucine supplementation on muscle protein synthesis and degradation pathways in broilers at constant dietary concentrations of isoleucine and valine.

The present study investigated the hypothesis that dietary concentrations of leucine (Leu) in excess of the breeder´s recommendations activates protein synthesis and decreases protein degradation in muscle of broilers. Day-old male Ross 308 broilers (n = 450) were phase-fed corn-soybean meal-based diets during starter (d 1-10), grower (d 11-22), and finisher (d 23-34) period. The basal diets fed to the control group (L0) met the broilers' requirements for nutrients and amino acids, and contained Leu, Leu:isoleucine (Ile) and Leu:valine (Val) ratios, close to those recommended by the breeder (Leu:Ile: 100:54, 100:52, 100:51; Leu:Val 100:64, 100:61, 100:58; in starter, grower and finisher diet, resp.). Basal diets were supplemented with Leu to exceed the breeder's recommendations by 35% (group L35) and 60% (group L60). Growth performance during 34 d, and carcass weights, and breast and thigh muscle weights on d 34 were similar among groups. Hepatic and muscle mRNA levels of genes involved in the somatotropic axis [growth hormone receptor, insulin-like growth factor (IGF)-1, IGF binding protein 2, IGF receptor] on d 34 were not influenced by Leu. In the breast muscle, relative mRNA abundances of genes involved in the mammalian target of rapamycin (mTOR) pathway of protein synthesis (mTOR, ribosomal p70 S6 kinase) and the ubiquitin-proteasome pathway of protein degradation (F-box only protein 32, Forkhead box protein O1, Muscle RING-finger protein-1) on d 34 were largely similar among groups. Likewise, relative phosphorylation and thus activation of mTOR and ribosomal protein S6 involved in the mTOR pathway, and of eukaryotic translation initiation factor 2A (eIF2a) involved in the general control nonderepressible 2 (GCN2)/eIF2a pathway of protein synthesis inhibition, were not influenced. These data indicate that dietary Leu concentrations exceeding the broiler´s requirements up to 60% neither influence protein synthesis nor degradation pathways nor muscle growth in growing broilers.

Effects of methionine on muscle protein synthesis and degradation pathways in broilers.

This study investigated the hypothesis that supplementation of methionine (Met) to broiler diets increases muscle growth due to regulation of molecular pathways related to protein synthesis and degradation depending on the Met source. Day-old male Cobb-500 broilers (n = 240) were phase-fed three different wheat-soya bean meal-based basal diets during days 1-10, 11-21 and 22-35. Basal diets (Met- group, Met + Cys concentration 15% below NRC recommendations) were supplemented with 0.10% or 0.40% Met either as DL-Met (DLM) or DL-2-hydroxy-4-(methylthio) butanoic acid (DL-HMTBA) (equimolar comparison). Breast muscle weights were lower in the Met- group compared to all Met-supplemented groups and were lower in broilers supplemented with 0.10% of DL-HMTBA compared to the other groups fed Met-supplemented diets. However, the expression of genes or relative phosphorylation and thus activation state of proteins involved in the somatotropic axis, the mammalian target of rapamycin (mTOR) pathway of protein synthesis, the ubiquitin-proteasome pathway (UPP) and autophagy-lysosomal pathway of protein degradation, the GCN2/eIF2a pathway involved in the inhibition of protein synthesis and in the myostatin-Smad2/3 pathway involved in myogenesis were not affected by Met source. Feeding diets with suboptimum Met + Cys concentrations, however, decreased expression of GHR and IGF1 in liver and muscle and increased that of MURF1 involved in the UPP in the broiler's muscle at day 10 and 21, while that of FOXO and atrogin-1 and FOXO phosphorylation remained unaffected. Additionally, suboptimum dietary Met concentrations increased expression of the autophagy-related genes ATG5 and BECN1 at day 35. Met supplementation neither affected gene expression nor phosphorylation of proteins involved in the GNC2/eIF2a and mTOR pathways. These data indicate that protein synthesis was not affected on the molecular level, while protein degradation was marginally affected by dietary Met dosage.

Exercise training reverses inflammation and muscle wasting after tobacco smoke exposure.

Long-term cigarette smoking induces inflammatory processes in the pulmonary system that are suggested to "spill over" into systemic inflammation. Regular exercise has been shown to have anti-inflammatory properties. The aim of the study was to investigate the effects of therapeutic exercise on inflammation and muscle wasting in smoke-exposed mice. C57BL/6J mice ( n = 30) were separated into three groups to receive either 1) no specific treatment (control group), 2) 8-mo exposure to cigarette smoke [smoke-exposed (SE) group], or 3) 8 mo of cigarette smoke combined with exercise training during the last 2 mo (SEex group). The inflammatory status was analyzed by quantifying levels of various plasma proteins using multiplex ELISA and detection of lymphocyte surface markers by flow cytometry. Muscle tissue was analyzed by histological techniques and measurements of RNA/protein expression. SE led to decreased maximal O2 uptake (V̇o2max) and maximal running speed ( Vmax), which was reversed by exercise ( P < 0.05). Expression of ICAM-1, VCAM-1, and CD62L on T cells increased and was reversed by exercise ( P < 0.05). Similarly, SE induced an increase of various inflammatory cytokines, which were downregulated by exercise. In muscle, exercise improved the structure, oxidative capacity, and metabolism by reducing ubiquitin proteasome system activation, stimulating insulin-like growth factor 1 expression, and the SE-induced inhibition of mammalian target of rapamycin signaling pathway ( P < 0.05). Exercise training reverses smoke-induced decline in exercise capacity, systemic inflammation, and muscle wasting by addressing immune-regulating, anabolic, and metabolic pathways.

Basic mechanisms of the regulation of L-carnitine status in monogastrics and efficacy of L-carnitine as a feed additive in pigs and poultry.

A great number of studies have investigated the potential of L-carnitine as feed additive to improve performance of different monogastric and ruminant livestock species, with, however, discrepant outcomes. In order to understand the reasons for these discrepant outcomes, it is important to consider the determinants of L-carnitine status and how L-carnitine status is regulated in the animal's body. While it is a long-known fact that L-carnitine is endogenously biosynthesized in certain tissues, it was only recently recognized that critical determinants of L-carnitine status, such as intestinal L-carnitine absorption, tissue L-carnitine uptake, endogenous L-carnitine synthesis and renal L-carnitine reabsorption, are regulated by specific nutrient sensing nuclear receptors. This review aims to give a more in-depth understanding of the basic mechanisms of the regulation of L-carnitine status in monogastrics taking into account the most recent evidence on nutrient sensing nuclear receptors and evaluates the efficacy of L-carnitine as feed additive in monogastric livestock by providing an up-to-date overview about studies with L-carnitine supplementation in pigs and poultry.

Regulation of carnitine status in ruminants and efficacy of carnitine supplementation on performance and health aspects of ruminant livestock: a review.

Carnitine has long been known to play a critical role for energy metabolism. Due to this, a large number of studies have been carried out to investigate the potential of supplemental carnitine in improving performance of livestock animals including ruminants, with however largely inconsistent results. An important issue that has to be considered when using carnitine as a feed additive is that the efficacy of supplemental carnitine is probably dependent on the animal's carnitine status, which is affected by endogenous carnitine synthesis, carnitine uptake from the gastrointestinal tract and carnitine excretion. The present review aims to summarise the current knowledge of the regulation of carnitine status and carnitine homeostasis in ruminants, and comprehensively evaluate the efficacy of carnitine supplementation on performance and/or health in ruminant livestock by comparing the outcomes of studies with carnitine supplementation in dairy cattle, growing and finishing cattle and sheep. While most of the studies show that supplemental carnitine, even in ruminally unprotected form, is bioavailable in ruminants, its effect on either milk or growth performance is largely disappointing. However, supplemental carnitine appears to be a useful strategy to offer protection against ammonia toxicity caused by consumption of high levels of non-protein N or forages with high levels of soluble N both, in cattle and sheep.

["Stay and play" in football : Art of keeping players fit to play]. / "Stay and play" im Fußball : Die Kunst, den Spieler spielfähig zu halten.

Many publications about the treatment and return to play after severe football injuries are available from the scientific literature, particularly about injuries requiring surgery. In contrast, less severe football injuries, such as muscle strains, ankle sprains and contusions, are less well addressed in the literature although these represent the most frequent type of injury. Additionally, such reports often have a low level of evidence and guidelines on treatment and the return to play process are very rare. Thus, the time away from football and the timing of return to play after minor injuries depends on the experience and skills of the responsible medical team. To achieve the aim of stay and play on the field, the medical team should be highly knowledgeable in interdisciplinary football medicine, prevention strategies, first aid on the field, clinical and manual diagnostics, tissue regeneration, symptomatic and conservative treatment as well as in return to play decision-making. No consensus exists on stay and play procedures neither on the practical level nor on the scientific level regarding injury definition, the diagnostic and treatment options and stay and play criteria. Therefore, this article presents the first steps for assessing stay and play strategies after minor injuries to standardize and improve practical routine, education and scientific research.