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1.
Biomedicines ; 11(12)2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38137523

RESUMO

The objective of this study was to investigate whether the impairment of farnesoid X receptor (FXR)-fibroblast growth factor 19 (FGF19) signaling in juvenile pigs with non-alcoholic fatty liver disease (NAFLD) is associated with changes in the composition of the enterohepatic bile acid pool. Eighteen 15-day-old Iberian pigs, pair-housed in pens, were allocated to receive either a control (CON) or high-fructose, high-fat (HFF) diet. Animals were euthanized in week 10, and liver, blood, and distal ileum (DI) samples were collected. HFF-fed pigs developed NAFLD and had decreased FGF19 expression in the DI and lower FGF19 levels in the blood. Compared with the CON, the HFF diet increased the total cholic acid (CA) and the CA to chenodeoxycholic acid (CDCA) ratio in the liver, DI, and blood. CA and CDCA levels in the DI were negatively and positively correlated with ileal FGF19 expression, respectively, and blood levels of FGF19 decreased with an increasing ileal CA to CDCA ratio. Compared with the CON, the HFF diet increased the gene expression of hepatic 12-alpha-hydrolase, which catalyzes the synthesis of CA in the liver. Since CA species are weaker FXR ligands than CDCA, our results suggest that impairment of FXR-FGF19 signaling in NAFLD pigs is associated with a decrease in FXR agonism in the bile acid pool.

2.
Brain Sci ; 12(9)2022 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-36138929

RESUMO

The objective of this study was to investigate the effect of dietary fatty acid (FA) saturation and carbon chain length on brain bile acid (BA) metabolism and neuronal number in a pig model of pediatric NAFLD. Thirty 20-day-old Iberian pigs, pair-housed in pens, were randomly assigned to receive one of three hypercaloric diets for 10 weeks: (1) lard-enriched (LAR; n = 5 pens), (2) olive-oil-enriched (OLI, n = 5), and (3) coconut-oil-enriched (COC; n = 5). Pig behavior and activity were analyzed throughout the study. All animals were euthanized on week 10 and frontal cortex (FC) samples were collected for immunohistochemistry, metabolomic, and transcriptomic analyses. Data were analyzed by multivariate and univariate statistics. No differences were observed in relative brain weight, neuronal number, or cognitive functioning between diets. Pig activity and FC levels of neuroprotective secondary BAs and betaine decreased in the COC and OLI groups compared with LAR, and paralleled the severity of NAFLD. In addition, OLI-fed pigs showed downregulation of genes involved in neurotransmission, synaptic transmission, and nervous tissue development. Similarly, COC-fed pigs showed upregulation of neurogenesis and myelin repair genes, which caused the accumulation of medium-chain acylcarnitines in brain tissue. In conclusion, our results indicate that secondary BA levels in the FCs of NAFLD pigs are affected by dietary FA composition and are associated with metabolic and transcriptomic markers of brain injury. Dietary interventions that aim to replace saturated FAs by medium-chain or monounsaturated FAs in high-fat hypercaloric diets may have a negative effect on brain health in NAFLD patients.

3.
Animals (Basel) ; 12(15)2022 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-35892531

RESUMO

The skin is the first barrier the body has to protect itself from the environment. There are several bacteria that populate the skin, and their composition may change throughout the dog's life due to several factors, such as environmental changes and diseases. The objective of this research was to determine the skin microbiome changes due to a change in diet on healthy pet dogs. Healthy client-owned dogs (8) were fed a fresh diet for 30 days then dry foods for another 30 days after a 4-day transition period. Skin bacterial population samples were collected after each 30-day feeding period and compared to determine microbiome diversity. Alpha diversity was higher when dogs were fed the fresh diet compared to the dry foods. Additionally, feeding fresh food to dogs increased the proportion of Staphylococcus and decreased Porphyromonas and Corynebacterium. In conclusion, changing from fresh diet to dry foods promoted a relative decrease in skin microbiome in healthy pet dogs.

4.
Am J Physiol Endocrinol Metab ; 323(3): E187-E206, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35858244

RESUMO

The objective of this study was to investigate the effect of dietary fatty acid (FA) composition on bile acid (BA) metabolism in a pig model of NAFLD, by using a multiomics approach combined with histology and serum biochemistry. Thirty 20-day-old Iberian pigs pair-housed in pens were randomly assigned to receive 1 of 3 hypercaloric diets for 10 wk: 1) lard-enriched (LAR; n = 5 pens), 2) olive oil-enriched (OLI; n = 5), and 3) coconut oil-enriched (COC; n = 5). Animals were euthanized on week 10 after blood sampling, and liver, colon, and distal ileum (DI) were collected for histology, metabolomics, and transcriptomics. Data were analyzed by multivariate and univariate statistics. Compared with OLI and LAR, COC increased primary and secondary BAs in liver, plasma, and colon. In addition, both COC and OLI reduced circulating fibroblast growth factor 19, increased hepatic necrosis, composite lesion score, and liver enzymes in serum, and upregulated genes involved in hepatocyte proliferation and DNA repair. The severity of liver disease in COC and OLI pigs was associated with increased levels of phosphatidylcholines, medium-chain triacylglycerides, trimethylamine-N-oxide, and long-chain acylcarnitines in the liver, and the expression of profibrotic markers in DI, but not with changes in the composition or size of BA pool. In conclusion, our results indicate a role of dietary FAs in the regulation of BA metabolism and progression of NAFLD. Interventions that aim to modify the composition of dietary FAs, rather than to regulate BA metabolism or signaling, may be more effective in the treatment of NAFLD.NEW & NOTEWORTHY Bile acid homeostasis and signaling is disrupted in NAFLD and may play a central role in the development of the disease. However, there are no studies addressing the impact of diet on bile acid metabolism in patients with NAFLD. In juvenile Iberian pigs, we show that fatty acid composition in high-fat high-fructose diets affects BA levels in liver, plasma, and colon but these changes were not associated with the severity of the disease.


Assuntos
Ácidos e Sais Biliares , Gorduras na Dieta , Fígado , Hepatopatia Gordurosa não Alcoólica , Animais , Dieta Hiperlipídica , Ácidos Graxos , Humanos , Modelos Animais , Suínos
5.
Nutrients ; 13(12)2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34959747

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a serious metabolic condition affecting millions of people worldwide. A "Western-style diet" has been shown to induce pediatric NAFLD with the potential disruption of skeletal muscle composition and metabolism. To determine the in vivo effect of a "Western-style diet" on pediatric skeletal muscle fiber type and fuel utilization, 28 juvenile Iberian pigs were fed either a control diet (CON) or a high-fructose, high-fat diet (HFF), with or without probiotic supplementation, for 10 weeks. The HFF diets increased the total triacylglycerol content of muscle tissue but decreased intramyocellular lipid (IMCL) content and the number of type I (slow oxidative) muscle fibers. HFF diets induced autophagy as assessed by LC3I and LC3II, and inflammation, as assessed by IL-1α. No differences in body composition were observed, and there was no change in insulin sensitivity, but HFF diets increased several plasma acylcarnitines and decreased expression of lipid oxidation regulators PGC1α and CPT1, suggesting disruption of skeletal muscle metabolism. Our results show that an HFF diet fed to juvenile Iberian pigs produces a less oxidative skeletal muscle phenotype, similar to a detraining effect, and reduces the capacity to use lipid as fuel, even in the absence of insulin resistance and obesity.


Assuntos
Dieta da Carga de Carboidratos/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Frutose/administração & dosagem , Músculo Esquelético/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Animais , Dieta Ocidental/efeitos adversos , Modelos Animais de Doenças , Metabolismo Energético , Resistência à Insulina , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patologia , Músculo Esquelético/patologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Probióticos/administração & dosagem , Suínos , Triglicerídeos/metabolismo
6.
Animals (Basel) ; 11(11)2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34827908

RESUMO

Suinfort®, a commercial semen supplement demonstrated to increase fertility and litter size in commercial sows, was tested to improve reproductive performance in Iberian sows. A total of 1430 Iberian sows were artificially inseminated (AI) with semen from Duroc boars and assigned by parity to receive the seminal additive Suinfort® containing 2 IU oxytocin, 5 µg lecirelin, and 2 mM caffeine (SF; n = 1713 AI), or to serve as non-supplemented controls (CON; n = 2625 AI). CON showed a lower fertility comparing to winter for spring (p = 0.001) and summer (p < 0.001); summer was lower than autumn (p = 0.012). SF removed this seasonal effect (p > 0.05). Fertility was significantly higher for SF sows during summer (p = 0.025) and autumn (p = 0.004). Total born, live-born, stillborn, and mummified piglets did not differ between CON and SF but were impacted by the season, with total and live-born decreasing in summer compared with autumn (p < 0.001) and winter (p = 0.005). In conclusion, seminal supplementation with Suinfort® improved the fertility of Iberian sows during periods of seasonal infertility.

7.
Animals (Basel) ; 11(11)2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34828007

RESUMO

The Iberian pig is an autochthonous breed from the Iberian Peninsula highly valued for its meat. The sows are often bred as Iberian × Duroc crossings for increased efficiency. Since sow parity and season affect the reproductive performance, we evaluated two-year records from a commercial farrow-to-finish farm (live, stillborn, and mummified piglets after artificial insemination, AI). A total of 1293 Iberian sows were inseminated with semen from 57 boars (3024 AI). The effects of parity (gilts, 1, 2-4, 5-10, and >10 farrowings) and season were analyzed by linear mixed-effects models (LME). The data were fitted to cosinor models to investigate seasonal effects within parity groups. The effects of maximum daily temperature (MDT) and day length change (DLC) during spermatogenesis, pre-AI, and post-AI periods were analyzed with LME. The 2-4 group was the optimal one for parity. A seasonal effect was evident between spring-summer (lower fertility/prolificacy) and autumn-winter (higher). Cosinor showed that the seasonal drop in reproductive performance occurs earlier in Iberian sows than in other breeds, more evident in gilts. MDT negatively affected performance in all periods and DLC in spermatogenesis and pre-AI. These results are relevant for the improvement of Iberian sows' intensive farming.

8.
J Nutr ; 151(5): 1139-1149, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33693900

RESUMO

BACKGROUND: Fructose consumption has been linked to nonalcoholic fatty liver disease (NAFLD) in children. However, the effect of high-fructose corn syrup (HFCS) compared with sucrose in pediatric NAFLD has not been investigated. OBJECTIVES: We tested whether the isocaloric substitution of dietary sucrose by HFCS would increase the severity of NAFLD in juvenile pigs, and whether this effect would be associated with changes in gut histology, SCFA production, and microbial diversity. METHODS: Iberian pigs, 53-d-old and pair-housed in pens balanced for weight and sex, were randomly assigned to receive a mash diet top-dressed with increasing amounts of sucrose (SUC; n = 3 pens; 281.6-486.8 g/kg diet) or HFCS (n = 4; 444.3-724.8 g/kg diet) during 16 wk. Diets exceeded the animal's energy requirements by providing sugars in excess, but met the requirements for all other nutrients. Animals were killed at 165 d of age after blood sampling, and liver, muscle, and gut were collected for histology, metabolome, and microbiome analyses. Data were analyzed by multivariate and univariate statistics. RESULTS: Compared with SUC, HFCS increased subcutaneous fat, triacylglycerides in plasma, and butyrate in colon (P ≤ 0.05). In addition, HFCS decreased UMP and short-chain acyl carnitines in liver, and urea nitrogen and creatinine in serum (P ≤ 0.05). Microbiome analysis showed a 24.8% average dissimilarity between HFCS and SUC associated with changes in SCFA-producing bacteria. Body weight gain, intramuscular fat, histological and serum markers of liver injury, and circulating hormones, glucose, and proinflammatory cytokines did not differ between diets. CONCLUSIONS: Fructose consumption derived from HFCS promoted butyrate synthesis, triglyceridemia, and subcutaneous lipid deposition in juvenile Iberian pigs, but did not increase serum and histological markers of NAFLD compared with a sucrose-enriched diet. Longer studies could be needed to observe differences in liver injury among sugar types.


Assuntos
Adiposidade/efeitos dos fármacos , Sacarose Alimentar/efeitos adversos , Xarope de Milho Rico em Frutose/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/etiologia , Triglicerídeos/sangue , Animais , Sacarose Alimentar/administração & dosagem , Ácidos Graxos Voláteis/metabolismo , Feminino , Microbioma Gastrointestinal , Trato Gastrointestinal/anatomia & histologia , Trato Gastrointestinal/efeitos dos fármacos , Xarope de Milho Rico em Frutose/administração & dosagem , Masculino , Distribuição Aleatória , Suínos
9.
PLoS One ; 15(12): e0244013, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33320899

RESUMO

The generation of large metabolomic data sets has created a high demand for software that can fit statistical models to one-metabolite-at-a-time on hundreds of metabolites. We provide the %polynova_2way macro in SAS to identify metabolites differentially expressed in study designs with a two-way factorial treatment and hierarchical design structure. For each metabolite, the macro calculates the least squares means using a linear mixed model with fixed and random effects, runs a 2-way ANOVA, corrects the P-values for the number of metabolites using the false discovery rate or Bonferroni procedure, and calculate the P-value for the least squares mean differences for each metabolite. Finally, the %polynova_2way macro outputs a table in excel format that combines all the results to facilitate the identification of significant metabolites for each factor. The macro code is freely available in the Supporting Information.


Assuntos
Fígado/metabolismo , Metaboloma , Metabolômica/métodos , Software , Animais , Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/etiologia , Fígado Gorduroso/prevenção & controle , Fígado/microbiologia , Espectrometria de Massas/métodos , Probióticos/uso terapêutico , Suínos
10.
Amino Acids ; 52(9): 1319-1335, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32974749

RESUMO

When neonatal pigs continuously fed formula are supplemented with leucine pulses, muscle protein synthesis and body weight gain are enhanced. To identify the responsible mechanisms, we combined plasma metabolomic analysis with transcriptome expression of the transcriptome and protein catabolic pathways in skeletal muscle. Piglets (n = 23, 7-day-old) were fed continuously a milk replacement formula via orogastric tube for 21 days with an additional parenteral infusion (800 µmol kg-1 h-1) of either leucine (LEU) or alanine (CON) for 1 h every 4 h. Plasma metabolites were measured by liquid chromatography-mass spectrometry. Gene and protein expression analyses of longissimus dorsi muscle were performed by RNA-seq and Western blot, respectively. Compared with CON, LEU pigs had increased plasma levels of leucine-derived metabolites, including 4-methyl-2-oxopentanoate, beta-hydroxyisovalerate, ß-hydroxyisovalerylcarnitine, and 3-methylglutaconate (P ≤ 0.05). Leucine pulses downregulated transcripts enriched in the Kyoto Encyclopedia of Genes and Genomes terms "spliceosome," "GAP junction," "endocytosis," "ECM-receptor interaction," and "DNA replication". Significant correlations were identified between metabolites derived from leucine catabolism and muscle genes involved in protein degradation, transcription and translation, and muscle maintenance and development (P ≤ 0.05). Further, leucine pulses decreased protein expression of autophagic markers and serine/threonine kinase 4, involved in muscle atrophy (P ≤ 0.01). In conclusion, results from our studies support the notion that leucine pulses during continuous enteral feeding enhance muscle mass gain in neonatal pigs by increasing protein synthetic activity and downregulating protein catabolic pathways through concerted responses in the transcriptome and metabolome.


Assuntos
Suplementos Nutricionais , Leucina/farmacologia , Metaboloma/efeitos dos fármacos , Proteínas Musculares/metabolismo , Músculo Esquelético/citologia , Atrofia Muscular/patologia , Transcriptoma/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Feminino , Leucina/administração & dosagem , Proteínas Musculares/genética , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/metabolismo , Fosforilação , Suínos
11.
Am J Physiol Endocrinol Metab ; 319(3): E592-E606, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32744096

RESUMO

The objective of this study was to investigate whether juvenile Iberian pigs with diet-induced nonalcoholic fatty liver disease (NAFLD), cholestasis, and gut dysbiosis would develop histological and metabolic markers of neurodegeneration in the frontal cortex (FC) and whether supplementing probiotics would influence the response to the diet. Twenty-eight juvenile Iberian pigs were fed for 10 wk either a control (CON) or high-fructose high-fat (HFF) diet with or without a commercial probiotic mixture. Compared with CON, HFF-fed pigs had a decreased number of neurons and an increase in reactive astrocytes in FC tissue. There was also a decrease in one-carbon metabolites choline and betaine and a marked accumulation of bile acids, cholesteryl esters, and polyol pathway intermediates in FC of HFF-fed pigs, which were associated with markers of neurodegeneration and accentuated with the severity of NAFLD. Betaine depletion in FC tissue was negatively correlated with choline-derived phospholipids in colon content, whereas primary conjugated bile acids in FC were associated with cholestasis. Plasma kynurenine-to-tryptophan quotient, as a marker of indoleamine 2,3-dioxygenase activity, and intestinal dysbiosis were also correlated with neuronal loss and astrogliosis. Recognition memory test and FC levels of amyloid-ß and phosphorylated Tau did not differ between diets, whereas probiotics increased amyloid-ß and memory loss in HFF-fed pigs. In conclusion, our results show evidence of neurodegeneration in FC of juvenile Iberian pigs and establish a novel pediatric model to investigate the role of gut-liver-brain axis in diet-induced NAFLD.


Assuntos
Doenças Neurodegenerativas/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Animais , Colestase/metabolismo , Citocinas/metabolismo , Dieta , Dieta Hiperlipídica , Disbiose/metabolismo , Feminino , Lobo Frontal/metabolismo , Lobo Frontal/patologia , Frutose/efeitos adversos , Microbioma Gastrointestinal , Masculino , Atividade Motora , Doenças Neurodegenerativas/complicações , Doenças Neurodegenerativas/psicologia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/patologia , Probióticos , Desempenho Psicomotor , Suínos
12.
Animals (Basel) ; 10(3)2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32111041

RESUMO

At weaning, 33 mixed parity Hypor sows received either an injection of 400 IU equine chorionic gonadotrophin and 200 IU human chorionic gonadotrophin (hCG) (PG600; n = 13), PG600 with an additional 200 IU hCG 24 h later (Gn800; n = 11), or served as non-injected controls (n = 9). All gonadotrophin treated sows received an injection of 750 IU hCG at 80 h after weaning to induce ovulation (designated as time 0 h). At 0, 24, 36, 40, 44, 48, and 60 h, all sows were subject to transrectal ultrasonography to determine numbers and sizes of large (>6 mm) follicles and time of ovulation. The interval from injection of 750 IU hCG to ovulation was shorter in Gn800 compared to PG600 sows (p = 0.02), and more Gn800 sows had ≥9 preovulatory follicles compared to PG600 and controls (p = 0.02 and 0.003, respectively). Follicular cysts were evident in both PG600 and Gn800 sows.

13.
Am J Physiol Gastrointest Liver Physiol ; 318(3): G582-G609, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32003601

RESUMO

To investigate the role of bile acids (BAs) in the pathogenesis of diet-induced nonalcoholic steatohepatitis (NASH), we fed a "Western-style diet" [high fructose, high fat (HFF)] enriched with fructose, cholesterol, and saturated fat for 10 wk to juvenile Iberian pigs. We also supplemented probiotics with in vitro BA deconjugating activity to evaluate their potential therapeutic effect in NASH. Liver lipid and function, cytokines, and hormones were analyzed using commercially available kits. Metabolites, BAs, and fatty acids were measured by liquid chromatography-mass spectrometry. Histology and gene and protein expression analyses were performed using standard protocols. HFF-fed pigs developed NASH, cholestasis, and impaired enterohepatic Farnesoid-X receptor (FXR)-fibroblast growth factor 19 (FGF19) signaling in the absence of obesity and insulin resistance. Choline depletion in HFF livers was associated with decreased lipoprotein and cholesterol in serum and an increase of choline-containing phospholipids in colon contents and trimethylamine-N-oxide in the liver. Additionally, gut dysbiosis and hyperplasia increased with the severity of NASH, and were correlated with increased colonic levels of choline metabolites and secondary BAs. Supplementation of probiotics in the HFF diet enhanced NASH, inhibited hepatic autophagy, increased excretion of taurine and choline, and decreased gut microbial diversity. In conclusion, dysregulation of BA homeostasis was associated with injury and choline depletion in the liver, as well as increased biliary secretion, gut metabolism and excretion of choline-based phospholipids. Choline depletion limited lipoprotein synthesis, resulting in hepatic steatosis, whereas secondary BAs and choline-containing phospholipids in colon may have promoted dysbiosis, hyperplasia, and trimethylamine synthesis, causing further damage to the liver.NEW & NOTEWORTHY Impaired Farnesoid-X receptor (FXR)-fibroblast growth factor 19 (FGF19) signaling and cholestasis has been described in nonalcoholic fatty liver disease (NAFLD) patients. However, therapeutic interventions with FXR agonists have produced contradictory results. In a swine model of pediatric nonalcoholic steatohepatitis (NASH), we show that the uncoupling of intestinal FXR-FGF19 signaling and a decrease in FGF19 levels are associated with a choline-deficient phenotype of NASH and increased choline excretion in the gut, with the subsequent dysbiosis, colonic hyperplasia, and accumulation of trimethylamine-N-oxide in the liver.


Assuntos
Ácidos e Sais Biliares/metabolismo , Colina/metabolismo , Colo/metabolismo , Colo/microbiologia , Fatores de Crescimento de Fibroblastos/metabolismo , Microbioma Gastrointestinal , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Fatores Etários , Animais , Colo/patologia , Modelos Animais de Doenças , Disbiose , Feminino , Hiperplasia , Fígado/patologia , Masculino , Hepatopatia Gordurosa não Alcoólica/microbiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Probióticos/administração & dosagem , Transdução de Sinais , Sus scrofa
14.
J Pediatr Gastroenterol Nutr ; 70(5): e94-e99, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31990866

RESUMO

OBJECTIVES: Bile acid (BA) homeostasis is regulated by intestinal cellular signaling involving the farnesoid X receptor (FXR) and fibroblast growth factor 19 (FGF19) secretion. Using preterm and term pigs as a model, we examined postnatal changes in expression of the FXR-FGF19 axis that is poorly characterized in human infants. METHODS: Pigs delivered by caesarean section at 10-day preterm and near full term (115-day gestation) were fitted with orogastric and umbilical arterial catheters. Pigs were fed combined parenteral nutrition and minimal enteral nutrition for 5 days, followed by milk formula until 26 d days. Plasma and tissue samples were collected at days 0, 5, 11, and 26. Plasma FGF19 concentration and liver and distal intestinal gene expression of FGF19 and other FXR target genes were quantified. RESULTS: Plasma FGF19 levels were lower in preterm versus term newborn pigs (P < 0.05), increased markedly by 5 days, especially in preterm pigs, and decreased in both groups until day 26. Likewise, intestinal FXR and FGF19 expression was lower (P ≤ 0.05) in premature versus term newborn pigs and decreased (P ≤ 0.05) between days 5 and 26. Hepatic expression of cholesterol 7α-hydroxylase (CYP7A1) was inversely correlated with plasma FGF19 in both groups. CONCLUSIONS: We conclude that the activity of FXR-FGF19 axis is lower in preterm than in term newborn pigs but increases transiently and then declines by the first month of age. We also provide supportive evidence of negative feedback between plasma FGF19 and hepatic CYP7A1 expression.


Assuntos
Cesárea , Receptores Citoplasmáticos e Nucleares , Animais , Ácidos e Sais Biliares , Feminino , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Fígado/metabolismo , Gravidez , Receptores Citoplasmáticos e Nucleares/genética , Suínos , Regulação para Cima
15.
Brain Behav Immun ; 85: 46-56, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31026499

RESUMO

New generation, multicomponent parenteral lipid emulsions provide key fatty acids for brain growth and development, such as docosahexaenoic acid (DHA) and arachidonic acid (AA), yet the content may be suboptimal for preterm infants. Our aim was to test whether DHA and AA-enriched lipid emulsions would increase activity, growth, and neurodevelopment in preterm piglets and limit brain inflammation. Cesarean-delivered preterm pigs were given three weeks of either enteral preterm infant formula (ENT) or TPN with one of three parenteral lipid emulsions: Intralipid (IL), SMOFlipid (SMOF) or an experimental emulsion (EXP). Activity was continuously monitored and weekly blood sampling and behavioral field testing performed. At termination of the study, whole body and tissue metrics were collected. Neuronal density was assessed in sections of hippocampus (HC), thalamus, and cortex. Frontal cortex (FC) and HC tissue were assayed for fatty acid profiles and expression of genes of neuronal growth and inflammation. After 3 weeks of treatment, brain DHA content in SMOF, EXP and ENT pigs was higher (P < 0.01) in FC but not HC vs. IL pigs. There were no differences in brain weight or neuron density among treatment groups. Inflammatory cytokine TNFα and IL-1ß expression in brain regions were increased in IL pigs (P < 0.05) compared to other groups. Overall growth velocity was similar among groups, but IL pigs had higher percent body fat and increased insulin resistance compared to other treatments (P < 0.05). ENT pigs spent more time in higher physical activity levels compared to all TPN groups, but there were no differences in exploratory behavior among groups. We conclude that a soybean oil emulsion increased select brain inflammatory cytokines and multicomponent lipid emulsions enriched with DHA and AA in parenteral lipids results in increased cortical DHA and improved body composition without affecting short term neurodevelopmental outcomes.


Assuntos
Ácidos Docosa-Hexaenoicos , Recém-Nascido Prematuro , Animais , Composição Corporal , Encéfalo , Emulsões , Feminino , Óleos de Peixe , Humanos , Recém-Nascido , Azeite de Oliva , Gravidez , Óleo de Soja , Suínos , Triglicerídeos
16.
Animals (Basel) ; 9(10)2019 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-31569532

RESUMO

During the periods January to April, May to August, and September to December in two consecutive years, sows were assigned at breeding to receive semen doses supplemented with 87 µg cloprostenol (PG; n = 158), 5 IU oxytocin (OT; n = 154), 2 µg buserelin (GN; n = 93), or served as non-supplemented controls (CON; n = 605). Sows were inseminated at the detection of estrus, and again 24 h later, but only the first inseminations were supplemented. Compared to CON, only buserelin increased pregnancy and farrowing rates (p ≤ 0.05); there was no effect of a period or a treatment × period interaction. Litter size was larger (p ≤ 0.001) for all seminal additive groups during the first two periods and tended to increase in GN compared to CON (p ≤ 0.1) during the third period, resulting in a tendency (p < 0.1) for a period × treatment interaction. The addition of cloprostenol, oxytocin or buserelin to semen doses at first insemination increases litter size in multiparous sows.

17.
Anim Reprod Sci ; 210: 106193, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31635779

RESUMO

The objective of this study was to determine effects of a novel seminal supplement, SuinFort, on fertility of multiparous sows. For 2 years, a total of 1159 sows were assigned to be artificial inseminated (AI) either with semen supplemented with the additive (2 IU oxytocin, 5 µg lecirelin, 2 mM caffeine, n = 830 AI) or with no supplementation (Control, n = 2422 AI). The supplement was included 15 min before insemination. Supplementation with SuinFort resulted in greater fertility both by increasing farrowing rate 87.2% ± 0.7 to 90.7% ± 1.0 (P < 0.001) and litter size from 13.8 ± 0.1 to 14.4 ± 0.1 (P < 0.001). To test if there was a direct effect of SuinFort on spermatozoa, an in vitro experiment was conducted using semen doses from 10 boars. Semen was stored at 15 °C and on days 1, 2 and 3 were aliquoted to a control and SuinFort-supplemented group, incubated at 37 °C and analyzed for sperm quality at 15 min and 2 h. For aliquots with SuinFort, there was a small decrease in semen quality. In conclusion, the administration of a combination of oxytocin, lecirelin and caffeine to boar semen 15 min prior to AI, positively affects sow fertility. Considering that in vitro effects on sperm quality were small, it is likely that SuinFort affects fertility by modulating uterine function. Supplementation of semen with SuinFort, therefore, has potential for increasing pork production efficiency as a result of increased reproductive efficiency after AI of sows.


Assuntos
Fármacos para a Fertilidade Feminina/farmacologia , Inseminação Artificial/veterinária , Sêmen , Suínos/fisiologia , Animais , Cafeína/administração & dosagem , Cafeína/farmacologia , Criopreservação/veterinária , Quimioterapia Combinada , Feminino , Fármacos para a Fertilidade Feminina/administração & dosagem , Masculino , Oligopeptídeos/administração & dosagem , Oligopeptídeos/farmacologia , Ocitocina/administração & dosagem , Ocitocina/farmacologia , Gravidez , Análise do Sêmen , Preservação do Sêmen/veterinária
18.
Can J Vet Res ; 82(3): 239-242, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30026650

RESUMO

The objective of this study was to determine whether birth order influences piglet survival because of reduced uptake of maternal antibodies by the piglets born later in large litters. Forty-five litters were serially allocated to one of 2 study groups. The crèche group consisted of 18 litters for which the 205 piglets were removed to a warm box to prevent suckling until 4 h after delivery of the first pig, and the control group of 27 litters for which 306 piglets were allowed to suckle from birth. The protein content of piglet blood and sow colostrum was determined with Brix refractometers. Parity, farrowing duration, liveborn litter size, litter size at 12 d, and piglet weight at birth and at 24 h and 12 d of age did not differ between the 2 treatment groups (P > 0.1). There were also no significant differences (P > 0.1) at any time point in weight or in the mean percent protein in plasma between the first 3 and the last 3 piglets born to an individual sow. However, the mean percent protein in plasma was significantly higher in the control group than in the crèche group at both 24 h (P ≤ 0.05) and day 12 (P ≤ 0.01) postpartum. The lack of differences in plasma protein levels between the first and last pigs born along with the lower percent plasma protein in the piglets that were prevented from suckling immediately after birth militate against the use of this technique as a way to equalize the opportunity for adequate transfer of maternal antibodies.


L'objectif de la présente étude était de déterminer si l'ordre de naissance influence la survie des porcelets à cause de la réduction d'ingestion d'anticorps maternels par les porcelets nés plus tard dans les portées nombreuses. Quarante-cinq portées ont été réparties de manière successive à l'un des deux groupes d'étude. Le groupe crèche était constitué de 18 portées pour lesquelles les 205 porcelets ont été maintenus dans une boîte chauffée pour empêcher la tétée jusqu'à 4 h après la naissance du premier porcelet, et le groupe témoin de 27 portées pour lesquelles les 306 porcelets ont pu téter dès la naissance. Le contenu en protéine du sang des porcelets et du colostrum de la truie a été déterminé avec un réfractomètre Brix. La parité, la durée de la mise-bas, le nombre de porcelets nés vivants, la taille de la portée à 12 j, et le poids des porcelets à la naissance et à 24 h et 12 j d'âge n'étaient pas différents entre les deux groupes de traitement (P > 0,1). Il n'y avait également pas de différence significative (P > 0,1) à aucun des temps mesurés pour le poids ou le pourcentage moyen de protéines dans le plasma entre les trois premiers et les trois derniers porcelets nés à une truie individuelle. Toutefois, le pourcentage moyen en protéine dans le plasma était significativement plus élevé dans le groupe témoin que dans le groupe crèche à 24 h (P ≤ 0,05) et au jour 12 (P ≤ 0,01) post-partum. Le manque de différence dans les quantités de protéines plasmatiques entre le premier et le dernier né avec également le pourcentage de protéine plasmatique plus faible chez les porcelets qui ont été empêché de boire immédiatement après la naissance milite contre l'utilisation de cette technique comme moyen d'égaliser l'opportunité pour un transfert adéquat d'anticorps maternels.(Traduit par Docteur Serge Messier).


Assuntos
Animais Lactentes , Colostro , Ingestão de Alimentos , Comportamento Alimentar , Tamanho da Ninhada de Vivíparos , Suínos/fisiologia , Animais , Animais Recém-Nascidos , Proteínas Sanguíneas , Feminino , Lactação , Parto , Gravidez
19.
Am J Physiol Gastrointest Liver Physiol ; 315(4): G638-G649, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30048597

RESUMO

Necrotizing enterocolitis (NEC) is associated with low plasma arginine and vascular dysfunction. It is not clear whether low intestinal citrulline production, the precursor for arginine synthesis, occurs before and thus predisposes to NEC or if it results from tissue damage. This study was designed to test the hypothesis that whole body rates of citrulline, arginine, and nitric oxide synthesis are low in premature pigs and that they precede NEC. Piglets delivered by cesarean section at 103 days [preterm (PT)], 110 days [near-term (NT)], or 114 days [full-term (FT)] of gestation were given total parenteral nutrition and after 2 days orogastrically fed infant formula for 42 h to induce NEC. Citrulline and arginine fluxes were determined before and during the feeding protocol. Gross macroscopic and histological NEC scores and plasma fatty acid binding protein (iFABP) concentration were determined as indicators of NEC. Intestinal gene expression for enzymes of the arginine pathway were quantitated. A lower ( P < 0.05) survival rate was observed for PT (8/27) than for NT (9/9) and FT pigs (11/11). PT pigs had higher macroscopic gross ( P < 0.05) and histological NEC ( P < 0.05) scores and iFABP concentration ( P < 0.05) than pigs of more advanced gestational age. PT pigs had lower citrulline production and arginine fluxes ( P < 0.05) throughout and a reduced gene expression in genes of the citrulline-arginine pathway. In summary, intestinal enzyme expression and whole body citrulline and arginine fluxes were reduced in PT pigs compared with animals of more advance gestational age and preceded the development of NEC. NEW & NOTEWORTHY Arginine supplementation prevents necrotizing enterocolitis (NEC), the most common gastrointestinal emergency of prematurity. Citrulline (precursor for arginine) production is reduced during NEC, and this is believed to be a consequence of intestinal damage. In a swine model of NEC, we show that intestinal gene expression of the enzymes for citrulline production and whole body citrulline and arginine fluxes are reduced and precede the onset of NEC in premature pigs. Reduced citrulline production during prematurity may be a predisposition to NEC.


Assuntos
Arginina/metabolismo , Citrulina/metabolismo , Enterocolite Necrosante/etiologia , Desenvolvimento Fetal , Mucosa Intestinal/metabolismo , Óxido Nítrico/metabolismo , Animais , Enterocolite Necrosante/metabolismo , Enterocolite Necrosante/patologia , Mucosa Intestinal/crescimento & desenvolvimento , Mucosa Intestinal/patologia , Suínos
20.
Amino Acids ; 50(7): 943-959, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29728917

RESUMO

The objective of this study was to determine if enteral leucine or branched-chain amino acid (BCAA) supplementation increases muscle protein synthesis in neonates who consume less than their protein and energy requirements, and whether this increase is mediated via the upregulation of the mechanistic target of rapamycin complex 1 (mTORC1) pathway or the decrease in muscle protein degradation signaling. Neonatal pigs were fed milk replacement diets containing reduced energy and protein (R), R supplemented with BCAA (RBCAA), R supplemented with leucine (RL), or complete protein and energy (CON) at 4-h intervals for 9 (n = 24) or 21 days (n = 22). On days 9 and 21, post-prandial plasma amino acids and insulin were measured at intervals for 4 h; muscle protein synthesis rate and activation of mTOR-related proteins were determined at 120 min post-feeding in muscle. For all parameters measured, the effects of diet were not different between day 9 or day 21. Compared to CON and R, plasma leucine and BCAA were higher (P ≤ 0.01) in RL- and RBCAA-fed pigs, respectively. Body weight gain, protein synthesis, and activation of S6 kinase (S6K1), 4E-binding protein (4EBP1), and eukaryotic initiation factor 4 complex (eIF4E·eIF4G) were decreased in RBCAA, RL, and R relative to CON (P < 0.01). RBCAA and RL upregulated (P ≤ 0.01) S6K1, 4EBP1, and eIF4E·eIF4G compared to R. In conclusion, when protein and energy are restricted, both leucine and BCAA supplementation increase mTOR activation, but do not enhance skeletal muscle protein synthesis and muscle growth in neonatal pigs.


Assuntos
Aminoácidos de Cadeia Ramificada/farmacologia , Ração Animal , Leucina/farmacologia , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Animais , Animais Recém-Nascidos , Suínos
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