RESUMO
BACKGROUND: In rats, it has been observed that treatment with activators of peroxisome proliferator-activated receptor α (PPARα) disturbs metabolic adaptations during lactation, which in turn lead to a reduction of milk fat content and gains of litters during the suckling period. It has not yet been investigated whether agonists of PPARα are impairing milk production of lactating sows in a similar manner as in rats. Therefore, the present study aimed to investigate the effect of treatment with clofibrate, a strong synthetic agonist of PPARα, on milk composition and litter gains in lactating sows. RESULTS: Twenty lactating sows received either a basal diet (control group) or the same diet with supplementation of 2 g of clofibrate per kg of diet (clofibrate group). In the clofibrate group, mRNA concentrations of various PPARα target genes involved in fatty acid utilization in liver and skeletal muscle were moderately up-regulated. Fat and energy content of the milk and gains of litters during the suckling period were not different between the control group and the clofibrate group. CONCLUSION: It is shown that treatment with clofibrate induces only a moderate up-regulation of PPARα target genes in liver and muscle of lactating sows and in turn might have limited effect on whole body fatty acid utilization. This may be the reason why clofibrate treatment did not influence milk fat content and gains of litters during the suckling period. Thus, the present study indicates that activation of PPARα induced either by native agonists such as dietary polyunsaturated fatty acids or a by negative energy balance might be largely uncritical in lactating sows with respect to milk production and litter gains in lactating sows.
Assuntos
Animais Recém-Nascidos/crescimento & desenvolvimento , Clofibrato/farmacologia , Gorduras/análise , Lactação/efeitos dos fármacos , Leite/química , PPAR alfa/agonistas , Animais , Suplementos Nutricionais , Ácidos Graxos não Esterificados/sangue , Feminino , Proteínas do Leite/análise , Suínos , Triglicerídeos/sangue , Aumento de Peso/efeitos dos fármacosRESUMO
In rodents, forced activation of hepatic peroxisome proliferator-activated receptor α (PPARα) by administration of exogenous PPARα activators during lactation leads to a reduction of milk triacylglycerol (TAG) production. Herein, we investigated whether a negative energy balance (NEB) induced by feed restriction (about 18% lower feed and energy intake) during lactation by increasing the release of fatty acids, which act as PPARα agonists, causes a disruption of hepatic lipid metabolism and thereby impairs milk TAG production in sows. Nutrient and energy content of the milk on day 20 of lactation and gains of litters during the first 14 d and the whole 21 d suckling period did not differ between Control and feed-restricted sows. The mRNA concentrations of several sterol regulatory element-binding protein target genes involved in lipid synthesis in the liver and the plasma concentration of TAG were reduced in the feed-restricted sows, whereas the mRNA concentrations of PPARα target genes involved in fatty acid oxidation in liver and skeletal muscle were not different between groups. In conclusion, it was shown that an NEB during lactation does not adversely affect milk composition and gains of litters, despite inhibiting hepatic expression of genes involved in lipid synthesis and reducing plasma TAG concentration. The finding that PPARα target genes involved in fatty acid utilisation in liver and muscle of sows are not induced by the NEB during lactation may explain that fatty acid availability in the mammary gland is sufficient to maintain milk TAG production and to allow normal litter gain.
Assuntos
Ingestão de Energia , Metabolismo Energético , Metabolismo dos Lipídeos , Sus scrofa/fisiologia , Ração Animal/análise , Animais , Dieta/veterinária , Feminino , Lactação , Fígado/metabolismo , Leite , PPAR alfa/genética , PPAR alfa/metabolismo , Distribuição Aleatória , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Sus scrofa/genética , Sus scrofa/crescimento & desenvolvimentoRESUMO
High-producing sows develop typical signs of an inflammatory condition and endoplasmic reticulum (ER) stress in the liver during lactation. At present, it is unknown whether a negative energy balance (NEB) is causative for this. Therefore, an experiment with lactating sows, which were either restricted in their feed intake to 82% of their energy requirement (Group FR) or were fed to meet their energy requirement (Control), was performed and the effect on ER stress-induced unfolded protein response (UPR), nuclear factor kappa B (NF-κB), nuclear factor E2-related factor 2 (Nrf2) and NOD-like receptor P3 (NLRP3) inflammasome signalling in the liver was evaluated. Relative mRNA concentrations of several genes involved in ER stress-induced UPR, NF-κB and NLRP3 inflammasome signalling were reduced in the liver of Group FR compared to the Control group. Plasma concentrations of haptoglobin and C-reactive protein were 13% and 37%, respectively, lower in Group FR than in the Control group, but these differences were not significant. In conclusion, feed restriction in lactating sows inhibits pro-inflammatory and ER stress signalling pathways in the liver, which suggests that not the NEB per se is causative for inflammation and ER stress induction in the liver of lactating sows. Rather it is likely that ER stress during lactation is the consequence of the presence of potent pro-inflammatory and ER stress-inducing stimuli, such as cytokines, reactive oxygen species and microbial components, which enter the circulation as a result of infectious diseases that frequently occur in sows after farrowing.
Assuntos
Ração Animal/análise , Estresse do Retículo Endoplasmático , Metabolismo Energético , Inflamação/imunologia , Transdução de Sinais , Doenças dos Suínos/imunologia , Animais , Restrição Calórica , Dieta/veterinária , Feminino , Inflamação/etiologia , Inflamação/metabolismo , Lactação , Fígado/metabolismo , Músculo Esquelético/metabolismo , Suínos , Doenças dos Suínos/etiologia , Doenças dos Suínos/metabolismoRESUMO
Lactating sows have been shown to develop typical signs of an inflammatory condition in the liver during the transition from pregnancy to lactation. Hepatic inflammation is considered critical due to the induction of an acute phase response and the activation of stress signaling pathways like the endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR), both of which impair animal's health and performance. Whether ER stress-induced UPR is also activated in the liver of lactating sows and whether dietary fish oil as a source of anti-inflammatory effects n-3 PUFA is able to attenuate hepatic inflammation and ER stress-induced UPR in the liver of sows is currently unknown. Based on this, two experiments with lactating sows were performed. The first experiment revealed that ER stress-induced UPR occurs also in the liver of sows during lactation. This was evident from the up-regulation of a set of genes regulated by the UPR and numerically increased phosphorylation of the ER stress-transducer PERK and PERK-mediated phosphorylation of eIF2α and IκB. The second experiment showed that fish oil inhibits ER stress-induced UPR in the liver of lactating sows. This was demonstrated by decreased mRNA levels of a number of UPR-regulated genes and reduced phosphorylation of PERK and PERK-mediated phosphorylation of eIF2α and IκB in the liver of the fish oil group. The mRNA levels of various nuclear factor-κB-regulated genes encoding inflammatory mediators and acute phase proteins in the liver of lactating sows were also reduced in the fish oil group. In line with this, the plasma levels of acute phase proteins were reduced in the fish oil group, although differences to the control group were not significant. In conclusion, ER stress-induced UPR is present in the liver of lactating sows and fish oil is able to inhibit inflammatory signaling pathways and ER stress-induced UPR in the liver.
Assuntos
Estresse do Retículo Endoplasmático , Óleos de Peixe/metabolismo , Lactação , Fígado/metabolismo , Transdução de Sinais , Animais , Proteína C-Reativa/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fator de Iniciação 2 em Eucariotos/metabolismo , Feminino , Óleos de Peixe/farmacologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Proteínas I-kappa B/metabolismo , Inflamassomos/genética , Inflamassomos/metabolismo , Fígado/efeitos dos fármacos , Músculo Esquelético/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , RNA Mensageiro/genética , Transdução de Sinais/efeitos dos fármacos , Suínos , Resposta a Proteínas não Dobradas/genética , eIF-2 Quinase/metabolismoRESUMO
Brachyspira hyodysenteriae, the causative agent of swine dysentery, is responsible for severe mucohaemorrhagic colitis with considerable financial loss to worldwide swine production. Antimicrobial resistance against macrolides and lincosamides is widespread and the mechanisms are well known. Currently, the most common treatment for swine dysentery is the use of pleuromutilins and resistance to these drugs also is increasingly being reported. Although resistance mechanisms against pleuromutilins are less clear than for other drugs, they seem to involve alterations of the peptidyl transferase centre (PTC), including ribosomal RNA and the ribosomal protein L3. The present study was conducted to examine molecular mechanisms of resistance on a representative set of B. hyodysenteriae field strains with different resistance patterns. In total, we identified 24 single nucleotide polymorphisms (SNPs) in the 23S rRNA gene and genes of the ribosomal proteins L3, L4, L2 and L22. The SNP in the ribosomal protein gene L3 at position 443 led to an amino acid substitution of asparagine (Asn) by serine (Ser) at position 148, significantly associated with MICs for pleuromutilins. Based on this SNP a correct assignment of 71% of the strains with respect to a threshold of >0.625 µg tiamulin/ml was reached. Unexpectedly low MICs in some of the Asn-strains were explained by a second SNP at position 2535 of the 23S rRNA. Our results clearly show the associations between MICs for pleuromutilins and mutations in their binding site. A complete list of SNPs that influence MICs of B. hyodysenteriae strains is needed to enable the interpretation of future molecular susceptibility testing.
Assuntos
Antibacterianos/farmacologia , Brachyspira hyodysenteriae/genética , Farmacorresistência Bacteriana/genética , Mutação , Subunidades Ribossômicas Maiores de Bactérias/genética , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sítios de Ligação , Brachyspira hyodysenteriae/efeitos dos fármacos , Brachyspira hyodysenteriae/isolamento & purificação , Diterpenos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Compostos Policíclicos , Polimorfismo de Nucleotídeo Único , RNA Ribossômico 23S/genética , RNA Ribossômico 23S/metabolismo , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , Suínos , PleuromutilinasRESUMO
Different vaccination strategies against Mycoplasma hyopneumoniae have been adopted worldwide. Reports from the field indicate varying levels of protection among currently available vaccines. The goal of the present study was to compare the efficacies of three widespread commercial vaccination strategies against M. hyopneumoniae under field conditions. 20 farms were included. 14 farms used different single dose vaccines (vaccine 1 [V1], 8 herds; vaccine 2 [V2], 6 herds); another 6 farms (V3) used a two dose vaccination strategy. Gross lesions of 854 lungs and histopathology from 140 lungs were quantified, and a quantitative PCR was applied to detect M. hyopneumoniae and porcine circovirus 2 (PCV2) DNA in lung tissue (n=140). In addition, porcine reproductive and respiratory disease virus (PRRSV), swine influenza virus (SIV), Actinobacillus pleuropneumoniae, Haemophilus parasuis and Pasteurella multocida were tested by qualitative PCR. 53% of lungs were positive for M. hyopneumoniae. 55.9% of lungs showed macroscopic enzootic pneumonia (EP)-like lesions. Lung lesion scores (P<0.001) and M. hyopneumoniae-loads (P<0.008) differed significantly among the vaccination groups, with the most severe cases and highest amounts occurring in V1. Histological alterations differed (P<0.001) between V1 and V3. Lung lesion scores and histopathological changes were significantly correlated, with prevalence and load of M. hyopneumoniae indicating that the applied diagnostic tools are valuable in confirming the prevalence and severity of M. hyopneumoniae infections. Comparing different vaccination strategies against M. hyopneumoniae indicates varying levels of protection. M. hyopneumoniae is still a major problem despite the widely applied vaccination.
Assuntos
Vacinas Bacterianas/farmacologia , Pulmão/patologia , Mycoplasma hyopneumoniae/isolamento & purificação , Pneumonia Suína Micoplasmática/epidemiologia , Pneumonia Suína Micoplasmática/patologia , Vacinação/veterinária , Animais , Bactérias/isolamento & purificação , Carga Bacteriana/veterinária , Vacinas Bacterianas/administração & dosagem , Feminino , Alemanha/epidemiologia , Masculino , Pneumonia Suína Micoplasmática/prevenção & controle , Pneumonia Suína Micoplasmática/virologia , Prevalência , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Suínos , Vírus/isolamento & purificaçãoRESUMO
BACKGROUND: Convincing evidence exist that carnitine synthesis and uptake of carnitine into cells is regulated by peroxisome proliferator-activated receptor α (PPARA), a transcription factor which is physiologically activated during fasting or energy deprivation. Sows are typically in a negative energy balance during peak lactation. We investigated the hypothesis that genes involved in carnitine synthesis and uptake in the liver of sows are up-regulated during peak lactation. FINDINGS: Transcript levels of several PPARα target genes involved in fatty acid uptake (FABP4, SLC25A20), fatty acid oxidation (ACOX1, CYP4A24) and ketogenesis (HMGCS2, FGF21) were elevated in the liver of lactating compared to non-lactating sows (P < 0.05). In addition, transcript levels of genes involved in carnitine synthesis (ALDH9A1, TMLHE, BBOX1) and carnitine uptake (SLC22A5) in the liver were greater in lactating than in non-lactating sows (P < 0.05). Carnitine concentrations in liver and plasma were about 20% and 50%, respectively, lower in lactating than in non-lactating sows (P < 0.05), which is likely due to an increased loss of carnitine via the milk. CONCLUSIONS: The results of the present study show that PPARα is activated in the liver of sows during lactation which leads to an up-regulation of genes involved in carnitine synthesis and carnitine uptake. The PPARα mediated up-regulation of genes involved in carnitine synthesis and uptake in the liver of lactating sows may be regarded as an adaptive mechanism to maintain hepatic carnitine levels at a level sufficient to transport excessive amounts of fatty acids into the mitochondrion.
Assuntos
Carnitina/biossíntese , Carnitina/metabolismo , Lactação/fisiologia , Suínos/genética , Regulação para Cima/fisiologia , Animais , Transporte Biológico/genética , Transporte Biológico/fisiologia , Feminino , Lactação/genéticaRESUMO
The present study aimed to explore the lactation-induced changes in hepatic gene expression in sows (Sus scrofa) during lactation. Using a porcine whole-genome microarray a total of 632 differentially expressed genes in the liver of lactating compared to non-lactating sows could be identified. Enrichment analysis revealed that the differentially expressed genes were mainly involved in fatty acid metabolism, pyruvate metabolism, glutathione metabolism, glycine, serine and threonine metabolism, citrate cycle, glycerophospholipid metabolism, PPAR signaling, and focal adhesion. The most striking observation with respect to intermediary metabolism was that genes involved in fatty acid catabolism, the catabolism of gluconeogenic amino acids, the citrate cycle and the respiratory chain were up-regulated in the liver of sows during lactation. With respect to immune response, it could be demonstrated that genes encoding acute phase proteins and genes involved in tissue repair were up-regulated and genes encoding adhesion molecules were down-regulated in the liver of sows during lactation. The results indicate that energy-generating pathways and pathways involved in the delivery of gluconeogenic substrates are induced in sow liver during lactation. The alterations of expression of genes encoding proteins involved in immune response suggest that lactation in sows may cause an adaptive immune response that possibly counteracts hepatic inflammation.
Assuntos
Imunidade Adaptativa/genética , Perfilação da Expressão Gênica , Lactação , Fígado/metabolismo , RNA Mensageiro/genética , Suínos/imunologia , Animais , Sequência de Bases , Primers do DNA , Regulação para Baixo , Feminino , Reação em Cadeia da Polimerase em Tempo Real , Suínos/genéticaRESUMO
BACKGROUND: It has recently been shown that the lactation-induced inflammatory state in the liver of dairy cows is accompanied by activation of the nuclear factor E2-related factor 2 (Nrf2) pathway, which regulates the expression of antioxidant and cytoprotective genes and thereby protects tissues from inflammatory mediators and reactive oxygen species (ROS). The present study aimed to study whether the Nrf2 pathway is activated also in the liver of lactating sows. FINDINGS: Transcript levels of known Nrf2 target genes, UGT1A1 (encoding glucuronosyltransferase 1 family, polypeptide A1), HO-1 (encoding heme oxygenase 1), NQO1 (encoding NAD(P)H dehydrogenase, quinone 1), GPX1 (encoding glutathione peroxidase), PRDX6 (encoding peroxiredoxin 6), TXNRD1 (encoding thioredoxin reductase 1), and SOD (encoding superoxide dismutase), in the liver are significantly elevated (between 1.7 and 3.1 fold) in lactating sows compared to non-lactating sows. The inflammatory state in the liver was evidenced by the finding that transcript levels of genes encoding acute phase proteins, namely haptoglobin (HP), fibrinogen γ (FGG), complement factor B (CFB), C-reactive protein (CRP) and lipopolysaccharide-binding protein (LBP), were significantly higher (2 to 8.7 fold) in lactating compared to non-lactating sows. CONCLUSIONS: The results of the present study indicate that the Nrf2 pathway in the liver of sows is activated during lactation. The activation of Nrf2 pathway during lactation in sows might be interpreted as a physiologic means to counteract the inflammatory process and to protect the liver against damage induced by inflammatory signals and ROS.
Assuntos
Regulação da Expressão Gênica , Fígado/metabolismo , Fator 2 Relacionado a NF-E2/genética , Transdução de Sinais , Sus scrofa/fisiologia , Proteínas de Fase Aguda/genética , Proteínas de Fase Aguda/metabolismo , Animais , Feminino , Lactação , Fator 2 Relacionado a NF-E2/metabolismo , Oxirredução , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Transcrição GênicaRESUMO
Surgical castration of young male piglets is now a generally accepted cause of serious distress and impairment of animal welfare. Awareness of this problem has created the moral commitment to seek for practical and more humane alternatives. As one possible alternative, the application of analgesics has been installed in Germany as an interim solution by the QS system, thus mandatory for the majority of German pig producers.Two analgesics have been authorised for this purpose. Both have been shown a significant positive impact on cortisol levels if administered pre-operatively. However, their effects on pain, stress and discomfort during castration, and on the post-castration period are conflicting. Thus, the aim of the present study was to compare the effects of Meloxicam and Flunixin on cortisol levels, behavioural indices, vocalisation, and wound healing of surgical castrated piglets in the field. There was no difference in vocalisation during castration in analgesic treated and untreated piglets. Piglets castrated under analgesia still had significantly elevated serum cortisol levels 30 min post castration, when compared to the sham castrated group. Both analgesics led to a significant impairment of behavioural indices and wound healing. It is concluded that analgesics can improve the welfare of piglets during the first part of the post-castration period. However, the benefits may be considered small and may not meet the requirements of the EU. Hence it is of high importance to prevent the interim practice of surgical castration of male piglets under analgesics from becoming implemented as a permanent condition in pig production.
Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Clonixina/análogos & derivados , Orquiectomia/veterinária , Dor/veterinária , Tiazinas/uso terapêutico , Tiazóis/uso terapêutico , Animais , Comportamento Animal/efeitos dos fármacos , Clonixina/uso terapêutico , Hidrocortisona/sangue , Masculino , Meloxicam , Orquiectomia/efeitos adversos , Dor/tratamento farmacológico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/veterinária , Estresse Fisiológico/efeitos dos fármacos , Vocalização Animal/efeitos dos fármacos , Cicatrização/efeitos dos fármacosRESUMO
Lawsonia (L.) intracellularis, Brachyspira (B.) hyodysenteriae and B. pilosicoli are important pathogens in domestic pig production world-wide, responsible for porcine intestinal adenomatosis, swine dysentery, and porcine intestinal spirochetosis, respectively. Conventional PCR is the major diagnostic tool in the detection of the three pathogens, but the sole detection of bacterial DNA might lead to misinterpretations of results with respect to their clinical relevance, especially with mixed infections. Thus, the present study targeted the detection and quantification of the three pathogens in samples from herds with a case history of diarrhoea. Herds and samples were selected by the practitioners on a voluntary basis. Results were based on 1176 individual samples from 95 herds from Southern Germany. The pathogens were detected simultaneously by multiplex real-time PCR. The overall prevalence for L. intracellularis, B. hyodysenteriae and B. pilosicoli was 12.6%, 8.4% and 3.2% in faecal samples and 48.4%, 24.2% and 31.6% in herds, respectively. Sixty one percent, 82.6%, and 73.4% of herds positive for L. intracellularis, B. hyodysenteriae, and B. pilosicoli, respectively, had mixed infections. Median log values of DNA equivalents/g of faeces for L. intracellularis, B. hyodysenteriae and B. pilosicoli were 3.3, 5.9 and 3.2, with maxima of 8.3, 8.0 and 6.3, respectively. Within herd prevalence of B. hyodysenteriae and B. pilosicoli as well as the load of B. hyodysenteriae were significantly associated with the severity of diarrhoea.
Assuntos
Brachyspira/crescimento & desenvolvimento , Infecções por Desulfovibrionaceae/veterinária , Infecções por Bactérias Gram-Negativas/veterinária , Lawsonia (Bactéria)/crescimento & desenvolvimento , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/microbiologia , Animais , Carga Bacteriana/veterinária , Brachyspira/genética , Brachyspira hyodysenteriae/genética , Brachyspira hyodysenteriae/crescimento & desenvolvimento , DNA Bacteriano/análise , Infecções por Desulfovibrionaceae/epidemiologia , Infecções por Desulfovibrionaceae/microbiologia , Diarreia/epidemiologia , Diarreia/microbiologia , Diarreia/veterinária , Fezes/microbiologia , Feminino , Alemanha/epidemiologia , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Lawsonia (Bactéria)/genética , Masculino , Prevalência , SuínosRESUMO
Domestic pig herds in some regions of Germany are permanently threatened by Classical Swine Fever. In the case of suspicion, a series of infectious and non infectious causes has to be excluded. The present paper describes a case of Escherichia coli septicaemia, with clinical and pathological symptoms that could not be differentiated from European or African Swine Fever. The E. coli strain could not be classified by standard serotyping. Virulence factors common for ETEC (enterotoxic E. coli) or EDEC (edema-disease E. coli) were not detected. Instead, we found P-fimbriae and aerobactin, thus characterising this strain as an extraintestinal pathogenic strain. Such strains have sporadicly been reported as the cause of septicaemia in piglets or weaners, but the present case is the first report of an E. coli-associated septicaemia in an adult pig. This case shows that extraintestinal pathogenic E. coli can be the cause of severe septicaemia and haemorrhagia. They thus have to be considered as a further differential diagnosis in swine fever.