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1.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(8): 1155-1164, 2020 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-32895178

RESUMO

OBJECTIVE: To investigate the inhibitory effect of ketogenic diet (KD) on growth of neuroblastoma in mice. METHODS: BALB/c-nu mouse models bearing neuroblastoma xenografts were established by subcutaneous injection of human neuroblastoma cell line (SH-SY5Y). When the tumor volume reached 250 mm3, the mice were randomized into SD group with standard diet and PBS treatment, KD group with ketogenic diet and PBS treatment, and CP+KD group with ketogenic diet and cyclophosphamide (60 mg·kg-1·day-1) treatment, n=8. The tumor volume, body weight, blood glucose, ketone body (ß-Hydroxybutyrate) levels, and hepatic steatosis in the mice were assessed. The expressions of caspase-3 and caspase-8 were detected by Western blotting, and Ki67 expresison was detected using immunohistochemistry (IHC). Transmission electron microscopy (TEM) was employed for the autophagosomes, and the autophagic protein Beclin1, LC3A/B and P62 were detected by IHC and Western blotting. RESULTS: On day 28 post tumor cell injection, the mice in KD and CP+KD groups could prolong the overall survival rates than that in SD group (P < 0.001). On day 22 post the injection, the tumor volume in KD group was smaller than that in SD group (P < 0.05); on 16, 19, and 22 day post the injection, the tumor volume in CP+KD group was smaller than that in SD group (P < 0.01). The mice in SD group showed greater body weight on day 19 and higher blood glucose level on day 13 post the injection than those in the other two groups (P < 0.05). Blood ketone level and hepatic steatosis score were higher and glucose ketone index (GKI) was lower in KD and CP+KD groups than those in SD group (all P < 0.05). The expressions of Ki67 and apoptotic proteins were detected in the tumor tissues of all groups. TEM revealed more autophagosomes in the tumor tissues of KD group than that of SD group. P62 expression was lowered (P < 0.01) and Beclin1 and LC3A/B expressions were up-regulated in the tumor tissues of KD group (P < 0.05), which is consisitent with IHC. CONCLUSIONS: KD has a strong anti-tumor effect in the xenograft mouse model possibly by regulating cell autophagy.


Assuntos
Dieta Cetogênica , Neuroblastoma , Ácido 3-Hidroxibutírico , Animais , Glicemia , Linhagem Celular Tumoral , Humanos , Camundongos , Camundongos Endogâmicos BALB C
2.
Bioresour Technol ; 315: 123885, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32721829

RESUMO

The aim of this work was to investigate the thermophilic bacterium Schelegelella thermodepolymerans DSM 15344 in terms of its polyhydroxyalkanoates (PHA) biosynthesis capacity. The bacterium is capable of converting various sugars into PHA with the optimal growth temperature of 55 °C; therefore, the process of PHA biosynthesis could be robust against contamination. Surprisingly, the highest yield was gained on xylose. Results suggested that S. thermodepolymerans possess unique xylose metabolism since xylose is utilized preferentially with the highest consumption rate as compared to other sugars. In the genome of S. thermodepolymerans DSM 15344, a unique putative xyl operon consisting of genes responsible for xylose utilization and also for its transport was identified, which is a unique feature among PHA producers. The bacterium is capable of biosynthesis of copolymers containing 3-hydroxybutyrate and also 3-hydroxyvalerate subunits. Hence, S.thermodepolymerans seems to be promising candidate for PHA production from xylose rich substrates.


Assuntos
Comamonadaceae , Poli-Hidroxialcanoatos , Ácido 3-Hidroxibutírico , Xilose
3.
Rev Bras Parasitol Vet ; 29(2): e002220, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32428186

RESUMO

This study aimed to evaluate the effects of Trichostrongylus colubriformis infection on the hemato-biochemical parameters, feed digestibility, and nitrogen balance in Santa Inês lambs. Eighteen three-month-old Santa Ines castrated male lambs (16.9 ± 1.43 kg of body weight) were randomly distributed in two experimental treatments: infected with T. colubriformis (I, n = 9) and uninfected (U, n = 9). The I group received a total of 45,000 L3 larvae of T. colubriformis (5,000 infective larvae, three times per week, for three weeks). During the experimental period, blood, feed digestibility, and nitrogen balance were evaluated. The I lambs showed a reduction in erythrocytes, hemoglobin, hematocrit, mean corpuscular volume, and total proteins, as well as an increase in platelets and eosinophils compared to those in the U group (p < 0.05). With the exception of total protein content, these values were within the normal range for the species. Furthermore, lower dry matter and organic matter digestibility were observed in the I lambs (p = 0.08). The present findings highlight that T. colubriformis infection has the potential to impair some hemato-biochemical parameters as well as feed digestibility in lambs, which could affect their productivity.


Assuntos
Proteínas Sanguíneas/análise , Sistema Digestório/parasitologia , Nitrogênio/análise , Ovinos/parasitologia , Tricostrongilose/parasitologia , Trichostrongylus/parasitologia , Ácido 3-Hidroxibutírico/sangue , Animais , Contagem de Células Sanguíneas/veterinária , Modelos Animais de Doenças , Índices de Eritrócitos/veterinária , Fezes/química , Fezes/parasitologia , Hemoglobinas/análise , Masculino , Nitrogênio/urina , Soroalbumina Bovina/análise , Soroglobulinas/análise , Doenças dos Ovinos/parasitologia , Tricostrongilose/sangue , Tricostrongilose/urina , Tricostrongilose/veterinária
4.
Zhongguo Zhong Yao Za Zhi ; 45(5): 1142-1148, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32237458

RESUMO

Serum metabonomic profiles of the model of focal cerebral ischemia reperfusion is established with the suture-occluded method by Longa to study the effect of ginsenosides. In this study, 48 rats were randomly divided into six groups: sham-operated group, pathological model group, positive drug group(6 mg·kg~(-1)·d~(-1)) and high, medium, low-dose ginsenosides groups(200, 100, 50 mg·kg~(-1)·d~(-1)). They are given intragastric administration respectively with same amount of 0.5% CMC-Na,nimodipine and ginsenoside for 5 days. At 2 h after the final administration, the model was established with the suture-occluded method, and free radical-scavenging activity changes of ginsenoside were observed by maillard reaction, and Longa was possible used as a renoprotective agent-occluded method. At the end of 24 h after the reperfusion, the hemolymph of rats in each group was collected, and the ~1H-NMR spectrum was collected after being treated by certain methods, and analyzed by principal component analysis(PCA). Compared with sham-operated group, pathological model group showed significant increases in the levels of lactate, glutamate, taurine, choline, glucose and methionine, but decreases in the levels of 3-hydroxybutyrate and phosphocreatine/creatine in serum. After treatment with ginsenosides, lipid, 3-hydroxybutyrate and phosphocreatine/creatine were increased in the serum of ginsenosides group rats, but with decreases in lactate and glutamate. The results showed that ginsenosides could regulate metabolic disorders in rats with focal cerebral ischemia reperfusion, and promote a recovery in the process of metabolism. It's helpful to promote the metabolic changes in rats with focal cerebral ischemia reperfusion via ~1H-NMR, and lay a foundation to develop ginsenosides as a new drug to treat ischemic cerebral paralysis.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Ginsenosídeos/farmacologia , Metaboloma , Traumatismo por Reperfusão/tratamento farmacológico , Ácido 3-Hidroxibutírico , Animais , Isquemia Encefálica/metabolismo , Creatina , Hemolinfa , Fosfocreatina , Espectroscopia de Prótons por Ressonância Magnética , Distribuição Aleatória , Ratos , Traumatismo por Reperfusão/metabolismo
5.
Int J Sports Med ; 41(9): 603-609, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32252101

RESUMO

The ergogenic effect of caffeine is well established, although no investigations providing a high carbohydrate feeding strategy (pre-exercise meal=2 g/kg BM) co-ingested with caffeine exist for soccer. This investigation examines the effect of caffeine in addition to a pre-exercise carbohydrate meal and drink mid-way through a soccer simulation. Eight recreational soccer players completed an 85-minute soccer simulation followed by an exercise capacity test (Yo-yo Intermittent Endurance test level 2) on two occasions. Prior to exercise participants consumed a high carbohydrate meal, with placebo or 5 mg/kg BM-1 caffeine. No significant performance effect was identified (p=0.099) despite a 12.8% (109 m) improvement in exercise capacity following caffeine. Rates of carbohydrate and fat oxidation did not differ between conditions and nor were differences apparent for plasma glucose, fatty acids, glycerol, ß-hydroxybutyrate (p>0.05). However, an increase in lactate was observed for caffeine (p=0.039). A significant condition effect on rating of perceived exertion was identified (p<0.001), with the overall mean for the protocol lowered to 11.7±0.9 au for caffeine compared to 12.8±1.3 au. Caffeine supplementation with a carbohydrate feeding strategy failed to affect metabolic and metabolite responses, although reductions in perception of exercise were observed. While a 12.8% increase in exercise capacity was noted the findings were not significant, possibly due to the small sample size.


Assuntos
Desempenho Atlético/fisiologia , Cafeína/administração & dosagem , Dieta da Carga de Carboidratos , Exercício Físico/fisiologia , Substâncias para Melhoria do Desempenho/administração & dosagem , Futebol/fisiologia , Ácido 3-Hidroxibutírico/sangue , Glicemia/metabolismo , Carboidratos da Dieta/sangue , Método Duplo-Cego , Metabolismo Energético , Ácidos Graxos/sangue , Glicerol/sangue , Humanos , Ácido Láctico/sangue , Masculino , Percepção/fisiologia , Esforço Físico/fisiologia , Adulto Jovem
6.
Gene ; 745: 144647, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32247738

RESUMO

AIMS: Post-translational modifications (PTMs) of histones are regulated by the availability of their respective acyl-CoAs. Among these histone PTMs, the metabolic origin of histone butyrylation (Kbu) is still poorly understood. MATERIAL AND METHODS: The impact of starvation on the levels of Kbu was determined by western blotting on histones extracted from the liver of fed and fasted C57BL/6 mice and immunohistochemistry on liver paraffin sections. KEY FINDINGS: Using animal model we provide evidence that the stimulation of ketogenesis following starvation, in addition to histone beta-hydroxybutyrylation (Kbhb), also leads to an increase in histone butyrylation (Kbu). Using an immunohistochemistry (IHC) approach we report first that hepatocytes contained butyrylated histones with important cell-to-cell heterogeneity. More importantly, our investigations based on western blotting and IHC also proposed that the basal levels of Kbu differ between male and female mice, with female mouse hepatocytes containing higher levels of butyrylated histones. Starvation enhanced solely histone Kbu levels in the liver of males but not females. SIGNIFICANCE: This is the first demonstration of a sex-dependent large-scale stimulation of histone acylation. Our data also point to different basal metabolic conditions of the male and female liver cells with a sex-dependent impact on the hepatocytes' epigenome.


Assuntos
Histonas/metabolismo , Fígado/patologia , Lisina/metabolismo , Processamento de Proteína Pós-Traducional , Inanição/patologia , Ácido 3-Hidroxibutírico/metabolismo , Acil Coenzima A/metabolismo , Acilação , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Hepatócitos/patologia , Código das Histonas , Humanos , Corpos Cetônicos/metabolismo , Fígado/citologia , Masculino , Camundongos , Fatores Sexuais
7.
J Dairy Sci ; 103(5): 4795-4805, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32113768

RESUMO

Negative energy balance in dairy cows in early lactation is related to alteration of metabolic status. However, the relationships among energy balance, metabolic profile in plasma, and metabolic profile in milk have not been reported. In this study our aims were: (1) to reveal the metabolic profiles of plasma and milk by integrating results from nuclear magnetic resonance (NMR) with data from liquid chromatography triple quadrupole mass spectrometry (LC-MS); and (2) to investigate the relationship between energy balance and the metabolic profiles of plasma and milk. For this study 24 individual dairy cows (parity 2.5 ± 0.5; mean ± standard deviation) were studied in lactation wk 2. Body weight (mean ± standard deviation; 627.4 ± 56.4 kg) and milk yield (28.1 ± 6.7 kg/d; mean ± standard deviation) were monitored daily. Milk composition (fat, protein, and lactose) and net energy balance were calculated. Plasma and milk samples were collected and analyzed using LC-MS and NMR. From all plasma metabolites measured, 27 were correlated with energy balance. These plasma metabolites were related to body reserve mobilization from body fat, muscle, and bone; increased blood flow; and gluconeogenesis. From all milk metabolites measured, 30 were correlated with energy balance. These milk metabolites were related to cell apoptosis and cell proliferation. Nine metabolites detected in both plasma and milk were correlated with each other and with energy balance. These metabolites were mainly related to hyperketonemia; ß-oxidation of fatty acids; and one-carbon metabolism. The metabolic profiles of plasma and milk provide an in-depth insight into the physiological pathways of dairy cows in negative energy balance in early lactation. In addition to the classical indicators for energy balance (e.g., ß-hydroxybutyrate, acetone, and glucose), the current study presents some new metabolites (e.g., glycine in plasma and milk; kynurenine, panthothenate, or arginine in plasma) in lactating dairy cows that are related to energy balance and may be of interest as new indicators for energy balance.


Assuntos
Bovinos/metabolismo , Metabolismo Energético , Lactação/metabolismo , Metaboloma , Leite/metabolismo , Ácido 3-Hidroxibutírico/sangue , Tecido Adiposo/metabolismo , Animais , Peso Corporal , Dieta/veterinária , Metabolismo Energético/fisiologia , Feminino , Glucose/metabolismo , Lactose/análise , Gravidez
8.
J Dairy Sci ; 103(5): 4806-4821, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32173013

RESUMO

This study applied a quantitative proteomics approach along with bioinformatics analyses to investigate changes in the plasma proteome of normal and overconditioned dairy cows during the transition period. Fifteen weeks before their anticipated calving date, 38 multiparous Holstein cows were selected based on their current and previous body condition scores (BCS) and allocated to either a high or a normal BCS group (19 cows each). They received different diets until dry-off to reach targeted differences in BCS and back fat thickness (BFT) until dry-off. At dry-off, normal BCS cows had a BCS <3.5 (minimum, 2.75) and BFT <1.2 cm (minimum, 0.58), and the high BCS cows had a BCS >3.75 (maximum, 4.50) and BFT >1.4 cm (maximum, 2.90). The proteomics study used a subset of 5 animals from each group. These cows were selected based on their circulating concentrations of fatty acids (FA) on d 14 postpartum and ß-hydroxybutyrate (BHB) on d 21 postpartum, representing the greater or the lower extreme values within their BCS group, respectively. The high BCS subset (HE-HBCS) had 4.50 < BCS > 3.75, FA = 1.17 ± 0.46 mmol/L, and BHB = 2.15 ± 0.42 mmol/L (means ± SD), and the low BCS subset (LE-NBCS) had 3.50 < BCS > 2.75, FA = 0.51 ± 0.28 mmol/L, and BHB = 0.84 ± 0.17 mmol/L. Plasma samples from d -49, +7, and +21 relative to parturition were used for proteome profiling by applying the quantitative tandem mass tags (TMT) approach. Nondepleted plasma samples were subjected to reduction and digestion and then labeled with TMT 10plex reagents. High-resolution liquid chromatography-tandem mass spectrometry analysis of TMT-labeled peptides was carried out, and the acquired spectra were analyzed for protein identification and quantification. In total, 254 quantifiable proteins (criteria: 2 unique peptides and 5% false discovery rate) were identified in the plasma samples. From these, 24 differentially abundant proteins (14 more abundant, 10 less abundant) were observed in the LE-NBCS cows compared with the HE-HBCS cows during the transition period. Plasma α-2-macroglobulins were more abundant in HE-HBCS versus LE-NBCS cows at d +7 and +21. Gene Ontology enrichment analyses of differentially abundant proteins revealed that the acute inflammatory response, regulation of complement activation, protein activation cascade, and regulation of humoral immune response were the most enriched terms in the LE-NBCS group compared with the HE-HBCS group. In addition, we identified 24 differentially abundant proteins (16 in the LE-NBCS group, and 8 in the HE-HBCS group) during the transition period. The complement components C1q and C5 were less abundant, while C3 and C3d were more abundant in LE-NBCS compared with HE-HBCS cows. Overall, overconditioning around calving was associated with alterations in protein pathways related to acute inflammatory response and regulation of complement and coagulation cascades in transition cows.


Assuntos
Bovinos/sangue , Lactação/sangue , Proteoma , Ácido 3-Hidroxibutírico/sangue , Animais , Dieta/veterinária , Feminino , Perfilação da Expressão Gênica , Nível de Saúde , Redes e Vias Metabólicas , Leite/química , Parto , Gravidez
9.
Anim Sci J ; 91(1): e13329, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32219931

RESUMO

The aim of this study was to investigate the effect of different feeding methods on blood biochemical parameters by using a total of 32 Japanese Black breeding cows. The diet (silage) was distributed at a rough estimate for 18 days (FN period), and stanchions were not used in this period. After the FN period, the cows were separated in stanchions for feeding and were fed specified amount of silage by using scales on a feeder wagon, which was determined according to the diet formulation and average body weight of cows, for 30 days (FW period). On the last day of the two experiment periods, the body weight of all cows was recorded and blood samples were collected from 10 randomly selected cows. ß-hydroxybutyric acid and albumin (Alb) levels were significantly higher after the FW period than after FN period. The variation of glucose, Alb, calcium and lactic acid was significantly smaller after the FW period. Several blood parameters of the FW period were approximately the appropriate range of a Japanese Black breeding herd in the dry period. Our results suggest that the feeding method by use of a stanchion and proper diet formulation affects blood biochemical parameters and improves nutritional conditions for breeding cows.


Assuntos
Ração Animal , Criação de Animais Domésticos/métodos , Fenômenos Fisiológicos da Nutrição Animal , Análise Química do Sangue , Cruzamento , Bovinos/sangue , Métodos de Alimentação/veterinária , Ácido 3-Hidroxibutírico/sangue , Animais , Cálcio/sangue , Feminino , Ácido Láctico/sangue , Albumina Sérica
10.
J Dairy Sci ; 103(4): 3505-3520, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32037174

RESUMO

This study aimed to investigate effects of pretransport diet (rearing milk vs. electrolytes), type of vehicle (open vs. conditioned truck), and transport duration (6 vs. 18 h) on physiological status of young calves upon arrival at the veal farm. A total of 368 calves were transported in 2 consecutive batches from a collection center to a veal farm. Blood samples were collected from calves before transport; immediately posttransport (T0); and 4, 24, and 48 h, and 1, 3, and 5 wk posttransport. Blood was analyzed for glucose, urea, lactate, nonesterified fatty acids (NEFA), ß-hydroxybutyrate (BHB), creatine kinase, albumin, total protein, osmolality, calcium, sodium, magnesium, and hematological variables. Body weight, rectal temperature, and skin elasticity were determined before and immediately posttransport. Blood glucose, NEFA, and urea concentrations at T0 showed an interaction between pretransport diet and transport duration. Milk-fed and electrolyte-fed calves transported for 18 h did not significantly differ in plasma glucose concentration or serum NEFA concentrations. However, after 6 h of transport, milk-fed calves had higher plasma glucose and lower serum NEFA concentrations (4.71 mmol/L and 586.5 µmol/L, respectively) than electrolyte-fed calves (3.56 mmol/L and 916 µmol/L, respectively). After 18 h of transport, milk-fed calves had lower urea concentrations (5.40 mmol/L) than electrolyte-fed calves (7.38 mmol/L). In addition, at T0, after 6 h of transport, milk-fed calves gained weight (Δ = 0.41 kg), whereas electrolyte-fed calves lost weight (Δ = -0.16 kg). After 18 h of transport, both milk-fed and electrolyte-fed calves showed body weight losses (Δ = -0.67 and -0.74 kg, respectively). Type of vehicle had a limited influence on blood parameters. Concentrations of NEFA and BHB reached the maximum values at T0 and then decreased until wk 5 posttransport. The increase in NEFA and BHB concentrations between prior to and just posttransport (T0) was less pronounced in calves transported for 6 h (746.1 µmol/L and 0.38 mmol/L, respectively) than in calves transported for 18 h (850.6 µmol/L and 0.50 mmol/L). Overall, the recovery rate of calves at the veal farm seemed rapid; all blood parameters returned to (below) pretransport values within 48 h posttransport. We concluded that feeding milk before short-term transport helps young veal calves cope with transport, whereas this is not the case during long-term transport.


Assuntos
Bovinos/fisiologia , Dieta/veterinária , Transportes , Ácido 3-Hidroxibutírico/metabolismo , Ração Animal , Animais , Glicemia/metabolismo , Peso Corporal , Bovinos/sangue , Ácidos Graxos não Esterificados/sangue , Nível de Saúde , Masculino , Carne Vermelha , Fatores de Tempo
11.
Am J Physiol Endocrinol Metab ; 318(4): E568-E578, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32101029

RESUMO

Fetal growth restriction (FGR) is associated with compromised growth and metabolic function throughout life. Intrauterine therapy of FGR with intra-amniotic insulin-like growth factor-1 (IGF1) enhances fetal growth and alters perinatal metabolism and growth in a sex-specific manner, but the adult effects are unknown. We investigated the effects of intra-amniotic IGF1 treatment of FGR on adult growth and body composition, adrenergic sensitivity, and glucose-insulin axis regulation. Placental embolization-induced FGR was treated with four weekly doses of 360 µg intra-amniotic IGF1 (FGRI) or saline (FGRS). Offspring were raised to adulthood (18 mo: FGRI, n = 12 females, 12 males; FGRS, n = 13 females, 10 males) alongside offspring from unembolized and untreated sheep (CON; n = 12 females, 21 males). FGRI females had increased relative lean mass compared with CON but not FGRS (P < 0.05; 70.6 ± 8.2% vs. 61.4 ± 8.2% vs. 67.6 ± 8.2%), decreased abdominal adipose compared with CON and FGRS (P < 0.05; 43.7 ± 1.2% vs. 49.3 ± 0.9% vs. 48.5 ± 1.0%), increased glucose utilization compared with FGRS but not CON (P < 0.05; 9.6 ± 1.0 vs. 6.0 ± 0.9 vs. 7.6 ± 0.9 mg·kg-1·min-1), and increased ß-hydroxybutyric acid:nonesterified fatty acid ratio in response to adrenaline compared with CON and FGRS (P < 0.05; 3.9 ± 1.4 vs. 1.1 ± 1.4 vs. 1.8 ± 1.4). FGRS males were smaller and lighter compared with CON but not FGRI (P < 0.05; 86.8 ± 6.3 vs. 93.5 ± 6.1 vs. 90.7 ± 6.3 kg), with increased peak glucose concentration (10%) in response to a glucose load but few other differences. These effects of intra-amniotic IGF1 therapy on adult body composition, glucose-insulin axis function, and adrenergic sensitivity could indicate improved metabolic regulation during young adulthood in female FGR sheep.


Assuntos
Composição Corporal/efeitos dos fármacos , Retardo do Crescimento Fetal/tratamento farmacológico , Fator de Crescimento Insulin-Like I/uso terapêutico , Metabolismo/efeitos dos fármacos , Ácido 3-Hidroxibutírico/metabolismo , Absorciometria de Fóton , Animais , Epinefrina/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Glucose/metabolismo , Injeções , Insulina/metabolismo , Fator de Crescimento Insulin-Like I/administração & dosagem , Gravidez , Caracteres Sexuais , Ovinos , Embolização da Artéria Uterina , Útero
12.
J Dairy Sci ; 103(4): 3133-3146, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32059860

RESUMO

The objective was to investigate the effects of feed restriction on concentrations of selected milk metabolites in mid-lactation Holstein and Montbéliarde cows and to explore their correlations with energy balance and classic plasma and milk indicators of nutritional status. Eight Holstein and 10 Montbéliarde cows (165 ± 21 d in milk) underwent 6 d of feed restriction during which feed allowance was reduced to meet 50% of their net energy for lactation (NEL) requirements. The experiment was divided in 4 periods: control (CON; d -3 to -1), restriction (RES; d 1 to 6), wk 1 (W1; d 7 to 13), and wk 2 (W2; d 14 to 18) after refeeding at ad libitum intake. Intake, milk production, energy balance and plasma metabolites were used to validate the feed restriction model. Concentrations of 7 milk metabolites: ß-hydroxybutyrate (BHB), glucose, glucose-6-phosphate, isocitrate, glutamate, uric acid, and free amino groups were measured in morning milk samples, and fatty acids were measured in pooled p.m. and a.m. samples. Feed restriction induced a negative energy balance (-42.5 ± 4.4 MJ/d), increased plasma nonesterified fatty acids and BHB, and decreased plasma glucose concentrations. Feed restriction increased milk glucose-6-phosphate and isocitrate (+38% and +39%, respectively) and decreased milk BHB, glucose, glutamate, uric acid and free amino group concentrations (-20%, -57%, -65%, -42%, and -14%, respectively), compared with pre- restriction. Milk concentrations of medium-chain fatty acids (e.g., sum of C10 to C15) decreased and those of long chain (e.g., 18:0, cis-9 18:1) increased during restriction. Breed differences were not detected for the majority of variables. All studied milk metabolites were significantly correlated with energy balance (Spearman correlation = 0.48, 0.63, -0.31, -0.45, and 0.61 for BHB, glucose, glucose-6-phosphate, isocitrate, and glutamate, respectively). Milk glucose and glutamate showed the strongest correlations with plasma metabolites and milk FA associated with lipomobilization. These results suggest that milk metabolites may be used as noninvasive indicators of negative energy balance and metabolic status of dairy cows.


Assuntos
Ração Animal/análise , Bovinos/fisiologia , Metabolismo Energético , Leite/metabolismo , Ácido 3-Hidroxibutírico/sangue , Animais , Dieta/veterinária , Ácidos Graxos não Esterificados/sangue , Feminino , Glucose/metabolismo , Humanos , Lactação , Estado Nutricional
13.
Biochem Soc Trans ; 48(1): 51-59, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32096539

RESUMO

Much of the world's prominent and burdensome chronic diseases, such as diabetes, Alzheimer's, and heart disease, are caused by impaired metabolism. By acting as both an efficient fuel and a powerful signalling molecule, the natural ketone body, d-ß-hydroxybutyrate (ßHB), may help circumvent the metabolic malfunctions that aggravate some diseases. Historically, dietary interventions that elevate ßHB production by the liver, such as high-fat diets and partial starvation, have been used to treat chronic disease with varying degrees of success, owing to the potential downsides of such diets. The recent development of an ingestible ßHB monoester provides a new tool to quickly and accurately raise blood ketone concentration, opening a myriad of potential health applications. The ßHB monoester is a salt-free ßHB precursor that yields only the biologically active d-isoform of the metabolite, the pharmacokinetics of which have been studied, as has safety for human consumption in athletes and healthy volunteers. This review describes fundamental concepts of endogenous and exogenous ketone body metabolism, the differences between the ßHB monoester and other exogenous ketones and summarises the disease-specific biochemical and physiological rationales behind its clinical use in diabetes, neurodegenerative diseases, heart failure, sepsis related muscle atrophy, migraine, and epilepsy. We also address the limitations of using the ßHB monoester as an adjunctive nutritional therapy and areas of uncertainty that could guide future research.


Assuntos
Ácido 3-Hidroxibutírico/metabolismo , Ácido 3-Hidroxibutírico/uso terapêutico , Diabetes Mellitus/dietoterapia , Dieta Cetogênica , Suplementos Nutricionais , Epilepsia/dietoterapia , Jejum/metabolismo , Insuficiência Cardíaca/dietoterapia , Hepatócitos/metabolismo , Humanos , Doenças Neurodegenerativas/dietoterapia , Sepse/dietoterapia
14.
Animal ; 14(S1): s44-s54, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32024567

RESUMO

Aspects of neutrophil function are diminished or dysregulated in dairy cows in the weeks just before and after calving, which appears to be an important contributor to the occurrence of retained placenta, mastitis, metritis and endometritis. The timing and mechanisms by which specific elements of neutrophil function are impaired are only partially understood. Oxidative burst capacity is the element of neutrophil function most consistently shown to be impaired in the week after calving, but that observation may partially be biased because oxidative burst has been studied more than other functions. There is sufficient evidence to conclude that the availability of calcium and glucose, and exposure to elevated concentrations of non-esterified fatty acids or ß-hydroxybutyrate affect some aspects of neutrophil function. However, these factors have mostly been studied in isolation and their effects are not consistent. Social stressors such as a competitive environment for feeding or lying space should plausibly impair innate immune function, but when studied under controlled conditions such effects have generally not been produced. Similarly, treatment with recombinant bovine granulocyte colony-stimulating factor consistently produces large increases in circulating neutrophil count with modest improvements in function, but this does not consistently reduce the incidence of clinical diseases thought to be importantly attributable to impaired innate immunity. Research is now needed that considers the interactions among known and putative risk factors for impaired neutrophil function in dairy cows in the transition period.


Assuntos
Doenças dos Bovinos/imunologia , Endometrite/veterinária , Imunidade Inata , Mastite Bovina/imunologia , Placenta Retida/veterinária , Ácido 3-Hidroxibutírico/metabolismo , Adaptação Fisiológica , Animais , Bovinos , Endometrite/imunologia , Metabolismo Energético , Ácidos Graxos não Esterificados/metabolismo , Feminino , Fator Estimulador de Colônias de Granulócitos , Hipocalcemia , Lactação , Contagem de Leucócitos , Neutrófilos/metabolismo , Período Periparto , Placenta Retida/imunologia , Gravidez , Proteínas Recombinantes
15.
Biochem Med (Zagreb) ; 30(1): 010707, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32063730

RESUMO

Introduction: The measurement of ß-hydroxybutyrate (ßOHB) concentrations is a corner stone of the diagnosis of diabetic ketoacidosis and other ketonic states. The aim of this study was to perform a validation of a peripheral blood ßOHB assay (Randox) on a Roche cobas c502 analyser and to establish a ßOHB reference range for the validated assay. Materials and methods: Precision, linearity and limit of detection and blank (LoD, LoB) were determined according to Clinical and Laboratory Standards Institute (CLSI) EP05-A3, EP 06-A and EP17-A2 guidelines, using commercial control material and residual patient sample pools. As method comparison, for 190 semi-quantitative measurements of urine ketones we determined the corresponding ßOHB blood concentration. The reference range was based on the CLSI C28-A3 guideline, using 304 randomly selected serum samples from population based German National Cohort (GNC) study. Results: Coefficients of variation for the validated assay ranged from 1.5% for high concentrations (3.1 mmol/L) to 6.5% for low concentrations (0.1 mmol/L). Detection capacity was LoB = 0.011 mmol/L and LoD = 0.037 mmol/L. Linearity of the assay ranged from 0.10 to 3.95 mmol/L. The agreement between the semi-quantitative urine ketone test and the ßOHB blood test was moderate (Kappa = 0.66). The obtained 95% serum reference range was estimated as 0.02 to 0.28 mmol/l ßOHB. Conclusions: The Ranbut ßOHB assay showed good precision and analytical performance. Our results confirm that ßOHB measurement in peripheral blood is indeed a preferable alternative to the semi-quantitative measurement of urine ketones.


Assuntos
Ácido 3-Hidroxibutírico/sangue , Análise Química do Sangue/normas , Cetoacidose Diabética/sangue , Humanos , Valores de Referência
16.
J Dairy Sci ; 103(3): 2784-2799, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31980225

RESUMO

Maintaining metabolic balance is a key factor in the health of dairy cattle during the transition from pregnancy to lactation. Little is known regarding the role of the circadian timing system in the regulation of physiological changes during the transition period. We hypothesized that disruption of the cow's circadian timing system by exposure to chronic light-dark phase shifts during the prepartum period would negatively affect the regulation of homeostasis and cause metabolic disturbances, leading to reduced milk production in the subsequent lactation. The objective was to determine the effect of exposure to chronic light-dark phase shift during the last 5 wk prepartum of the nonlactating dry period on core body temperature, melatonin, blood glucose, ß-hydroxybutyric acid (BHB) and nonesterified fatty acid (NEFA) concentrations, and milk production. Multiparous cows were moved to tiestalls at 5 wk before expected calving and assigned to control (CTR; n = 16) or phase-shifted (PS; n = 16) treatments. Control cows were exposed to 16 h of light and 8 h of dark. Phase-shifted cows were exposed to the same photoperiod; however, the light-dark cycle was shifted 6 h every 3 d until parturition. Resting behavior and feed intake were recorded daily. Core body temperature was recorded vaginally for 48 h at 23 and 9 d before expected calving using calibrated data loggers. Blood concentrations of melatonin, glucose, BHB, and NEFA were measured during the pre- and postpartum periods. Milk yield and composition were measured through 60 DIM. Treatment did not affect feed intake or body condition. Cosine fit analysis of 24-h core body temperature and circulating melatonin indicated attenuation of circadian rhythms in the PS treatment compared with the CTR treatment. Phase-shifted cows had lower rest consolidation, as indicated by more total resting time, but shorter resting period durations. Phase-shifted cows had lower blood glucose concentration compared with CTR cows (4 mg/mL decrease), but BHB and NEFA concentrations were similar between PS and CTR cows. Milk yield and milk fat yield were greater in PS compared with CTR cows (2.8 kg/d increase). Thus, exposure to chronic light-dark phase shifts during the prepartum period attenuated circadian rhythms of core body temperature, melatonin, and rest-activity behavior and was associated with increased milk fat and milk yield in the postpartum period despite decreased blood glucose pre- and postpartum. Therefore, less variation in central circadian rhythms may create a more constant milieu that supports the onset of lactogenesis.


Assuntos
Glicemia/análise , Bovinos/fisiologia , Ritmo Circadiano , Leite/metabolismo , Ácido 3-Hidroxibutírico/sangue , Animais , Temperatura Corporal/efeitos da radiação , Dieta/veterinária , Ácidos Graxos não Esterificados/sangue , Feminino , Humanos , Insulina/sangue , Lactação , Melatonina/sangue , Leite/química , Parto/efeitos da radiação , Período Pós-Parto/efeitos da radiação , Gravidez
17.
FASEB J ; 34(1): 1412-1429, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31914599

RESUMO

Accumulation of amyloid ß (Aß) peptide, inflammation, and oxidative stress contribute to Alzheimer's disease (AD) and trigger complex pathogenesis. The ketone body ß-hydroxybutyrate (BHBA) is an endogenous metabolic intermediate that protects against stroke and neurodegenerative diseases, but the underlying mechanisms are unclear. The present study aims to elucidate the protective effects of BHBA in the early stage of AD model and investigate the underlying molecular mechanisms. Three-and-half-month-old double-transgenic mice (5XFAD) overexpressing ß-amyloid precursor protein (APP) and presenilin-1 (PS1) were used as the AD model. The 5XFAD mice received 1.5 mmol/kg/d BHBA subcutaneously for 28 days. Morris water maze test, nest construction, and passive avoidance experiments were performed to assess the therapeutic effects on AD prevention in vivo, and brain pathology of 5XFAD mice including amyloid plaque deposition and microglia activation were assessed. Gene expression profiles in the cortexes of 5XFAD- and BHBA-treated 5XFAD mice were performed with high-throughput sequencing and bioinformatic analysis. Mouse HT22 cells were treated with 2 mM BHBA to explore its in vitro protective effects of BHBA on hippocampal neurons against Aß oligomer toxicity, ATP production, ROS generation, and mitochondrial aerobic respiratory function. APP, BACE1, and neprilysin (NEP) expression levels were evaluated in HT22 cells following treatment with BHBA by measuring the presence or absence of G protein-coupled receptor 109A (GPR109A). BHBA improved cognitive function of 5XFAD mice in Morris water maze test, nesting construction and passive avoidance experiments, and attenuated Aß accumulation and microglia overactivation in the brain. BHBA also enhanced mitochondrial respiratory function of hippocampal neurons and protected it from Aß toxicity. The enzymes, APP and NEP were regulated by BHBA via G-protein-coupled receptor 109A (GPR109A). Furthermore, RNA sequencing revealed that BHBA-regulated genes mainly annotated in aging, immune system, nervous system, and neurodegenerative diseases. Our data suggested that BHBA confers protection against the AD-like pathological events in the AD mouse model by targeting multiple aspects of AD and it may become a promising candidate for the prevention and treatment of AD.


Assuntos
Ácido 3-Hidroxibutírico/farmacologia , Doença de Alzheimer/tratamento farmacológico , Cognição/efeitos dos fármacos , Hipocampo/metabolismo , Neurônios/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Linhagem Celular , Modelos Animais de Doenças , Regulação da Expressão Gênica , Hipocampo/patologia , Camundongos , Camundongos Transgênicos , Neurônios/patologia
18.
Can J Vet Res ; 84(1): 79-81, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31920219

RESUMO

The objective of this study was to evaluate the association between ketonemia and serum paraoxonase-1 (PON1), malondialdehyde (MDA), and other blood components in tail and mammary veins of dairy cows. Forty-two Holstein dairy cows with decreased feed intake were divided into HIGH (≥ 1.2 mM; n = 31) and LOW (< 1.2 mM; n = 11) groups based on the ß-hydroxybutyrate concentration in plasma collected from the tail vein. The HIGH group had a significantly greater plasma non-esterified fatty acid (NEFA) concentration, but significantly lower serum PON1 activity and phospholipid concentration, and a tendency to have a lower cholesterol ester concentration than the LOW group. Serum PON1 activity was not correlated with the MDA concentration but was positively correlated with serum concentrations of cholesterol esters and phospholipids, and negatively correlated with the plasma NEFA concentration. These results suggest that serum PON1 activity is reduced by hyperketonemia and the relevance of PON1 to MDA seems to not be direct, though it is involved.


Assuntos
Arildialquilfosfatase/sangue , Doenças dos Bovinos/enzimologia , Cetose/veterinária , Malondialdeído/sangue , Ácido 3-Hidroxibutírico/sangue , Animais , Análise Química do Sangue/veterinária , Bovinos , Doenças dos Bovinos/sangue , Ésteres do Colesterol/sangue , Colorimetria/veterinária , Ácidos Graxos não Esterificados/sangue , Feminino , Cetose/sangue , Cetose/enzimologia , Glândulas Mamárias Animais/irrigação sanguínea , Fosfolipídeos/sangue , Cauda/irrigação sanguínea
19.
J Dairy Sci ; 103(3): 2545-2555, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31928751

RESUMO

Hyperketonemia is a metabolic disease in dairy cows, associated with negative nutrition balance (NNB) induced by low dry matter intake (DMI) and increased nutrient requirements. Hyperketonemia could induce metabolic stress, which might indirectly affect mammary tissue. Autophagy is a highly conserved physiological process that results in the turnover of intracellular material, and is involved in maintaining cellular homeostasis under the challenge of metabolic stress induced by NNB. The aim of this study was to investigate the autophagy status and autophagy-related pathways AMP-activated kinase α (AMPKα) and mechanistic target of rapamycin (mTOR) in the mammary glands of dairy cows with hyperketonemia. Cows with hyperketonemia [CWH, n = 10, blood ß-hydroxybutyrate (BHB) concentration 1.2 to 3.0 mmol/L] and cows without hyperketonemia (CWOH, n = 10, BHB < 1.2 mmol/L) from 3 to 12 DIM were randomly selected from the herd. The mammary tissue and blood samples were collected from these cows between 0630 and 0800 h, before feeding, at 3 to 12 d in milk. Serum concentrations of glucose, BHB, and fatty acids were determined using an autoanalyzer with commercial kits between 0630 and 0800 h, before feeding. Concentrations of fatty acids, BHB (median and interquartile range: CWH, 2.44 and 1.3, 2.82 mM; CWOH, 0.49 and 0.41, 0.57 mM), and milk fat were greater in CWH. The DMI, glucose concentration, milk production, and milk protein levels were lower in CWH. The mRNA abundance of autophagosome formation-related gene, beclin 1 (BECN1), phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3), autophagy-related gene (ATG) 5, ATG7, ATG12, microtubule-associated protein 1 light chain 3 (MAP1LC3, also called LC3) and sequestosome-1 (SQSTM1, also called p62) were greater in the mammary glands of CWH. The protein abundance of LC3-II and phosphorylation level of Unc-51-like kinase 1 (ULK1) were greater in CWH, but the total ubiquitinated proteins and protein abundance of p62 were lower. Transmission electron microscopy showed an increased number of autophagosomes in the mammary glands of CWH. Furthermore, the phosphorylation of AMPKα was greater, but the phosphorylation of mTOR was lower in the mammary glands of CWH. These results indicate that activity of mTOR pathways and autophagy activity, and upregulation of AMPKα, may be response mechanisms to mitigate metabolic stress induced by hyperketonemia in the mammary glands of dairy cows.


Assuntos
Ácido 3-Hidroxibutírico/sangue , Proteínas Quinases Ativadas por AMP/metabolismo , Autofagossomos/metabolismo , Autofagia , Cetose/veterinária , Serina-Treonina Quinases TOR/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Animais , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Proteína Beclina-1 , Bovinos , Feminino , Glucose/metabolismo , Lactação , Fosforilação , Distribuição Aleatória , Serina-Treonina Quinases TOR/genética
20.
J Anim Sci ; 98(1)2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31917830

RESUMO

Periparturient diseases of dairy cows are caused by disproportionate energy metabolism, mineral imbalance, and perturbed immune function. The aim of the present study was to characterize metabolism, innate immune endometrial gene expression, and uterine microbial populations of transition animals receiving normal or restricted energy diets. Pregnant multiparous Holstein cows (n = 14) were randomly assigned to one of the two dietary treatments from 20 d prepartum until 35 d postpartum (DPP). One group was fed a diet providing 100% energy requirements (NE), whereas the other received an energy-restricted diet providing 80% energy requirements (RE). Feed intake, milk yield, body weight, body condition score, temperature, respiratory, and pulse rate were recorded. After calving, blood was collected weekly to analyze nonesterified fatty acids (NEFAs), ß-hydroxybutyrate (BHB), and total cholesterol (TC). Endometrial cytobrushes were collected for gene expression analysis of inflammatory markers, microbial populations determination, and cytological evaluation. The restricted energy diet did not alter feed intake or milk yield but changed energy balance and metabolites levels (P < 0.05). In fact, RE animals had high NEFA and BHB levels, and low TC concentrations (P < 0.05). Moreover, RE animals had upregulated gene expression of serum amyloid A3 (SAA3) at 35 DPP (P < 0.05) and CXC chemokine receptor 2 (CXCR2) at 14 DPP (P < 0.01). Interleukin (IL) 1 and IL8 genes were downregulated 14 DPP but upregulated 35 DPP in RE animals, whereas IL6 and lipopolysaccharide-binding protein (LBP) genes were upregulated at 14 DPP (P ≤ 0.05). The most abundant phyla in RE animals (n = 3) were Bacteroidetes and Fusobacteria, whereas Proteobacteria was the least abundant at both 14 and 35 DPP. In conclusion, it can be speculated that energy balance is one of the main drivers for uterine inflammation by affecting metabolism, immune function, and uterine microbiota. However, these findings should be validated in a larger sample size.


Assuntos
Bovinos/metabolismo , Dieta/veterinária , Ingestão de Energia/fisiologia , Metabolismo Energético , Ácido 3-Hidroxibutírico/sangue , Animais , Bactérias/genética , Peso Corporal , Bovinos/sangue , Colesterol/sangue , Dieta/normas , Metabolismo Energético/fisiologia , Ácidos Graxos não Esterificados/sangue , Feminino , Humanos , Lactação/fisiologia , Microbiota , Leite/química , Leite/metabolismo , Período Pós-Parto , Gravidez , RNA Ribossômico 16S/genética , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Transcrição Reversa , Útero/microbiologia , Útero/patologia
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