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1.
Sci Rep ; 12(1): 1825, 2022 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-35115578

RESUMO

Vitamin D is necessary for musculoskeletal health, however, the supplementation of vitamin D above the sufficiency level does not bring additional bone mass density (BMD), unlike physical exercise which enhances the bone formatting process. Regular physical activity has been shown to upregulate VDR expression in muscles and to increase circulating vitamin D. Here we investigate whether a single bout of exercise might change 25(OH)D3 blood concentration and how it affects metabolic response to exercise. Twenty-six boys, 13.8 years old (SD ± 0.7) soccer players, participated in the study. The participants performed one of two types of exercise: the first group performed the VO2max test until exhaustion, and the second performed three times the repeated 30 s Wingate Anaerobic Test (WAnT). Blood was collected before, 15 min and one hour after the exercise. The concentration of 25(OH)D3, parathyroid hormone (PTH), interleukin-6 (IL-6), lactate, non-esterified fatty acids (NEFA) and glycerol were determined. 25(OH)D3 concentration significantly increased after the exercise in all boys. The most prominent changes in 25(OH)D3, observed after WAnT, were associated with the rise of PTH. The dimensions of response to the exercises observed through the changes in the concentration of 25(OH)D3, PTH, NEFA and glycerol were associated with the significant increases of IL-6 level. A single bout of exercise may increase the serum's 25(OH)D3 concentration in young trained boys. The intensive interval exercise brings a more potent stimulus to vitamin D fluctuations in young organisms. Our results support the hypothesis that muscles may both store and release 25(OH)D3.


Assuntos
Calcifediol/sangue , Exercício Físico/fisiologia , Músculo Esquelético/fisiologia , Hormônio Paratireóideo/sangue , Aptidão Física/fisiologia , Adolescente , Atletas , Ácidos Graxos não Esterificados/sangue , Glicerol/sangue , Humanos , Interleucina-6/sangue , Ácido Láctico/sangue , Masculino , Projetos Piloto , Testes de Função Respiratória
2.
Nutrients ; 13(3)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652910

RESUMO

This study investigated the effect of decaffeinated green tea extract (dGTE), with or without antioxidant nutrients, on fat oxidation, body composition and cardio-metabolic health measures in overweight individuals engaged in regular exercise. Twenty-seven participants (20 females, 7 males; body mass: 77.5 ± 10.5 kg; body mass index: 27.4 ± 3.0 kg·m2; peak oxygen uptake (O2peak): 30.2 ± 5.8 mL·kg-1·min-1) were randomly assigned, in a double-blinded manner, either: dGTE (400 mg·d-1 (-)-epigallocatechin-3-gallate (EGCG), n = 9); a novel dGTE+ (400 mg·d-1 EGCG, quercetin (50 mg·d-1) and α-lipoic acid (LA, 150 mg·d-1), n = 9); or placebo (PL, n = 9) for 8 weeks, whilst maintaining standardised, aerobic exercise. Fat oxidation ('FATMAX' and steady state exercise protocols), body composition, cardio-metabolic and blood measures (serum glucose, insulin, leptin, adiponectin, glycerol, free fatty acids, total cholesterol, high [HDL-c] and low-density lipoprotein cholesterol [LDL-c], triglycerides, liver enzymes and bilirubin) were assessed at baseline, week 4 and 8. Following 8 weeks of dGTE+, maximal fat oxidation (MFO) significantly improved from 154.4 ± 20.6 to 224.6 ± 23.2 mg·min-1 (p = 0.009), along with a 22.5% increase in the exercise intensity at which fat oxidation was deemed negligible (FATMIN; 67.6 ± 3.6%O2peak, p = 0.003). Steady state exercise substrate utilisation also improved for dGTE+ only, with respiratory exchange ratio reducing from 0.94 ± 0.01 at week 4, to 0.89 ± 0.01 at week 8 (p = 0.004). This corresponded with a significant increase in the contribution of fat to energy expenditure for dGTE+ from 21.0 ± 4.1% at week 4, to 34.6 ± 4.7% at week 8 (p = 0.006). LDL-c was also lower (normalised fold change of -0.09 ± 0.06) for dGTE+ by week 8 (p = 0.038). No other significant effects were found in any group. Eight weeks of dGTE+ improved MFO and substrate utilisation during exercise, and lowered LDL-c. However, body composition and cardio-metabolic markers in healthy, overweight individuals who maintained regular physical activity were largely unaffected by dGTE.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Antioxidantes/administração & dosagem , Sobrepeso/terapia , Extratos Vegetais/administração & dosagem , Chá , Adiponectina/sangue , Adulto , Bilirrubina/sangue , Glicemia/efeitos dos fármacos , Composição Corporal/efeitos dos fármacos , Índice de Massa Corporal , Fatores de Risco Cardiometabólico , Colesterol/sangue , Método Duplo-Cego , Metabolismo Energético/efeitos dos fármacos , Enzimas/sangue , Exercício Físico/fisiologia , Ácidos Graxos não Esterificados/sangue , Feminino , Glicerol/sangue , Humanos , Insulina/sangue , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Sobrepeso/fisiopatologia , Oxirredução/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos
3.
J Sport Health Sci ; 10(2): 237-242, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33742603

RESUMO

BACKGROUND: Decaffeinated green tea extract (dGTE) can increase fat oxidation during leg exercise, but dGTE is unsuitable for many people (e.g., those with injuries/disabilities), and its effects on arm exercise and women are unknown. METHODS: Eight adults (23-37 years old, 4 women) performed an incremental arm cycle test to measure peak oxygen uptake (VO2peak), followed by four 1-h trials at 50% VO2peak. Subjects were randomly assigned to 650 mg of dGTE or placebo (PLA) for 4 weeks followed by a 4-week washout and crossover trial. Blood samples were obtained pre-exercise and post-exercise for glycerol and free fatty acid analysis. Respiratory gases were collected continuously. RESULTS: VO2 showed no differences across trials ((0.83-0.89) ± (0.19-0.25) L/min, p = 0.460), neither did energy expenditure ((264-266) ± (59-77) kcal, p = 0.420) nor fat oxidation (dGTE = 0.11 to 0.12 g/min vs. PLA = 0.10 to 0.09 g/min, p = 0.220). Fat oxidation as percentage of energy expenditure was not different for dGTE vs. PLA (23% ± 12% to 25% ± 11% vs. 23% ± 10% to 21% ± 9%, p = 0.532). Glycerol concentration increased post-exercise in all trials, independent of treatments (pre = (3.4-5.1) ± (0.6-2.6) mg/dL vs. post = (7.9-9.8) ± (2.6-3.7) mg/dL, p = 0.867, η2 = 0.005 for interaction), as did free fatty acid ((3.5-4.8) ± (1.4-2.2) mg/dL vs. (7.2-9.1) ± (2.6-4.5) mg/dL, p = 0.981, η2 = 0.000). CONCLUSION: Chronic dGTE supplementation had no effect on lipolysis and fat oxidation during arm cycle exercise in men and women.


Assuntos
Camellia sinensis/química , Exercício Físico , Lipólise/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Extratos Vegetais/farmacologia , Chá/química , Adulto , Braço , Estudos Cross-Over , Metabolismo Energético/efeitos dos fármacos , Ácidos Graxos não Esterificados/sangue , Feminino , Glicerol/sangue , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Placebos , Extratos Vegetais/administração & dosagem , Fatores de Tempo , Adulto Jovem
4.
J Dairy Sci ; 103(11): 10245-10257, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32921457

RESUMO

Pregnancy toxemia is the most frequent metabolic disorder of ewes in late pregnancy. Although propylene glycol (PG) and glycerol (GLY) are common glucogenic supplements for treating pregnancy toxemia in ewes, the relative benefit of these 2 supplements is not entirely clear. Therefore, the objectives of the present study were to determine the changes during 24 h in key blood metabolites and insulin in response to PG or GLY drenching in prolific ewes. To this end, 36 multiparous late-pregnant Afec-Assaf ewes (∼132.4 d pregnant) bearing 2 to 4 fetuses, divided into 2 blocks (18 ewes in each block), with a blood ß-hydroxybutyrate (BHB) concentration of 0.5 to 1.6 mmol/L were included. Ewes were divided into 3 groups (12 ewes each; 6 ewes in each experimental day), according to their BHB levels, expected litter size, body weight, and body condition score, and were drenched with the following: (1) control group (CTL), 55 mL of water; (2) PG, 106 mL of PG (100% PG, 448 calories); or (3) GLY, 108 mL of Koforin 80 (80% GL; 448 calories). Blood samples were taken before drenching and every hour after drenching for 24 h. Plasma concentration of glucose, BHB, nonesterified fatty acids, lactate, glycerol, and insulin were determined. Because there were no effects of treatments after 12 h in the first block, the data were analyzed for 12 h after drenching rather than 24 h. The plasma glucose concentration during the first 5 h after drenching was the highest in the GLY, BHB concentration was the lowest in the PG, and the nonesterified fatty acid levels were lower in the PG compared with the CTL ewes during the first 5 h after drenching. However, glucose concentration was higher in the PG ewes at 9, 11, and 12 h after drenching than in CTL or GLY ewes. The mean lactate concentration in plasma for 12 h was 2.5- and 1.9-fold higher in the PG compared with the CTL and GLY ewes, respectively, and except at 11 h after drenching, it was significantly higher at each time point. The insulin concentration was higher in the GLY than in both other groups at 2 to 5 h after drenching. These results suggest that during the first few hours after drenching the effect of PG was more effective in reducing the BHB concentration, whereas the GLY effect was more effective in enhancing glucose concentration. The increased concentration in lactate following PG treatment suggests that the PG contribution to gluconeogenesis is mediated through its metabolism to lactate. In contrast, the lack of an effect on lactate, and the faster increase in blood glucose in response to GLY suggest that GLY has a more advanced entry point to gluconeogenesis, which influences the immediate response in enhancing the glucose blood concentration.


Assuntos
Ácido 3-Hidroxibutírico/sangue , Glicemia/análise , Glicerol/administração & dosagem , Propilenoglicol/administração & dosagem , Ovinos/sangue , Animais , Suplementos Nutricionais , Ácidos Graxos não Esterificados/sangue , Feminino , Idade Gestacional , Gluconeogênese/efeitos dos fármacos , Glicerol/sangue , Insulina/sangue , Lactação/efeitos dos fármacos , Ácido Láctico/sangue , Pré-Eclâmpsia/prevenção & controle , Pré-Eclâmpsia/veterinária , Gravidez , Doenças dos Ovinos/prevenção & controle
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.
Am J Physiol Endocrinol Metab ; 318(4): E504-E513, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32069071

RESUMO

We hypothesized that probiotic supplementation (PRO) increases the absorption and oxidation of orally ingested maltodextrin during 2 h endurance cycling, thereby sparing muscle glycogen for a subsequent time trial (simulating a road race). Measurements were made of lipid and carbohydrate oxidation, plasma metabolites and insulin, gastrointestinal (GI) permeability, and subjective symptoms of discomfort. Seven male cyclists were randomized to PRO (bacterial composition given in methods) or placebo for 4 wk, separated by a 14-day washout period. After each period, cyclists consumed a 10% maltodextrin solution (initial 8 mL/kg bolus and 2 mL/kg every 15 min) while exercising for 2 h at 55% maximal aerobic power output, followed by a 100-kJ time trial. PRO resulted in small increases in peak oxidation rates of the ingested maltodextrin (0.84 ± 0.10 vs. 0.77 ± 0.09 g/min; P = 0.016) and mean total carbohydrate oxidation (2.20 ± 0.25 vs. 1.87 ± 0.39 g/min; P = 0.038), whereas fat oxidation was reduced (0.40 ± 0.11 vs. 0.55 ± 0.10 g/min; P = 0.021). During PRO, small but significant increases were seen in glucose absorption, plasma glucose, and insulin concentration and decreases in nonesterified fatty acid and glycerol. Differences between markers of GI damage and permeability and time-trial performance were not significant (P > 0.05). In contrast to the hypothesis, PRO led to minimal increases in absorption and oxidation of the ingested maltodextrin and small reductions in fat oxidation, whereas having no effect on subsequent time-trial performance.


Assuntos
Ciclismo/fisiologia , Metabolismo dos Carboidratos/efeitos dos fármacos , Suplementos Nutricionais , Probióticos/farmacologia , Adulto , Estudos Cross-Over , Carboidratos da Dieta , Método Duplo-Cego , Exercício Físico , Ácidos Graxos não Esterificados/sangue , Glucose/metabolismo , Glicerol/sangue , Humanos , Insulina/sangue , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Polissacarídeos/farmacocinética , Adulto Jovem
7.
Mol Genet Metab ; 125(3): 251-257, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30217721

RESUMO

INTRODUCTION: Glycerol phenylbutyrate (GPB) is approved in the US and EU for the chronic management of patients ≥2 months of age with urea cycle disorders (UCDs) who cannot be managed by dietary protein restriction and/or amino acid supplementation alone. GPB is a pre-prodrug, hydrolyzed by lipases to phenylbutyric acid (PBA) that upon absorption is beta-oxidized to the active nitrogen scavenger phenylacetic acid (PAA), which is conjugated to glutamine (PAGN) and excreted as urinary PAGN (UPAGN). Pharmacokinetics (PK) of GPB were examined to see if hydrolysis is impaired in very young patients who may lack lipase activity. METHODS: Patients 2 months to <2 years of age with UCDs from two open label studies (n = 17, median age 10 months) predominantly on stable doses of nitrogen scavengers (n = 14) were switched to GPB. Primary assessments included traditional plasma PK analyses of PBA, PAA, and PAGN, using noncompartmental methods with WinNonlin™. UPAGN was collected periodically throughout the study up to 12 months. RESULTS: PBA, PAA and PAGN rapidly appeared in plasma after GPB dosing, demonstrating evidence of GPB cleavage with subsequent PBA absorption. Median concentrations of PBA, PAA and PAGN did not increase over time and were similar to or lower than the values observed in older UCD patients. The median PAA/PAGN ratio was well below one over time, demonstrating that conjugation of PAA with glutamine to form PAGN did not reach saturation. Covariate analyses indicated that age did not influence the PK parameters, with body surface area (BSA) being the most significant covariate, reinforcing current BSA based dosing recommendations as seen in older patients. CONCLUSION: These observations demonstrate that UCD patients aged 2 months to <2 years have sufficient lipase activity to adequately convert the pre-prodrug GPB to PBA. PBA is then converted to its active moiety (PAA) providing successful nitrogen scavenging even in very young children.


Assuntos
Glicerol/análogos & derivados , Lipase/sangue , Fenilbutiratos/administração & dosagem , Pró-Fármacos/administração & dosagem , Distúrbios Congênitos do Ciclo da Ureia/tratamento farmacológico , Criança , Pré-Escolar , Feminino , Glutamina/sangue , Glicerol/administração & dosagem , Glicerol/sangue , Glicerol/farmacocinética , Humanos , Lactente , Masculino , Nitrogênio/sangue , Nitrogênio/metabolismo , Fenilacetatos/sangue , Fenilbutiratos/sangue , Fenilbutiratos/farmacocinética , Pró-Fármacos/farmacocinética , Distúrbios Congênitos do Ciclo da Ureia/sangue , Distúrbios Congênitos do Ciclo da Ureia/patologia
8.
Am J Physiol Endocrinol Metab ; 315(5): E1053-E1061, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30153067

RESUMO

An ethanolic extract of Artemisia scoparia (SCO) has metabolically favorable effects on adipocyte development and function in vitro and in vivo. In diet-induced obese mice, SCO supplementation significantly reduced fasting glucose and insulin levels. Given the importance of adipocyte lipolysis in metabolic health, we hypothesized that SCO modulates lipolysis in vitro and in vivo. Free fatty acids and glycerol were measured in the sera of mice fed a high-fat diet with or without SCO supplementation. In cultured 3T3-L1 adipocytes, the effects of SCO on lipolysis were assessed by measuring glycerol and free fatty acid release. Microarray analysis, qPCR, and immunoblotting were used to assess gene expression and protein abundance. We found that SCO supplementation of a high-fat diet in mice substantially reduces circulating glycerol and free fatty acid levels, and we observed a cell-autonomous effect of SCO to significantly attenuate tumor necrosis factor-α (TNFα)-induced lipolysis in cultured adipocytes. Although several prolipolytic and antilipolytic genes were identified by microarray analysis of subcutaneous and visceral adipose tissue from SCO-fed mice, regulation of these genes did not consistently correlate with SCO's ability to reduce lipolytic metabolites in sera or cell culture media. However, in the presence of TNFα in cultured adipocytes, SCO induced antilipolytic changes in phosphorylation of hormone-sensitive lipase and perilipin. Together, these data suggest that the antilipolytic effects of SCO on adipose tissue play a role in the ability of this botanical extract to improve whole body metabolic parameters and support its use as a dietary supplement to promote metabolic resiliency.


Assuntos
Adipócitos/efeitos dos fármacos , Artemisia , Lipólise/efeitos dos fármacos , Extratos Vegetais/farmacologia , Células 3T3-L1 , Adipócitos/metabolismo , Animais , Células Cultivadas , Ácidos Graxos não Esterificados/sangue , Glicerol/sangue , Camundongos , Perilipina-1/metabolismo , Fosforilação/efeitos dos fármacos , Esterol Esterase/metabolismo , Fator de Necrose Tumoral alfa/farmacologia
9.
Eur J Appl Physiol ; 118(6): 1265-1272, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29619595

RESUMO

PURPOSE: New Zealand blackcurrant (NZBC) extract has previously been shown to increase fat oxidation during prolonged exercise, but this observation is limited to males. We examined whether NZBC intake also increases fat oxidation during prolonged exercise in females, and whether this was related to greater concentrations of circulating fatty acids. METHODS: In a randomised, crossover, double-blind design, 16 endurance-trained females (age: 28 ± 8 years, BMI: 21.3 ± 2.1 kg·m-2, VO2max: 43.7 ± 1.1 ml·kg-1·min-1) ingested 600 mg·day-1 NZBC extract (CurraNZ™) or placebo (600 mg·day-1 microcrystalline cellulose) for 7 days. On day 7, participants performed 120 min cycling at 65% VO2max, using online expired air sampling with blood samples collected at baseline and at 15 min intervals throughout exercise for analysis of glucose, NEFA and glycerol. RESULTS: NZBC extract increased mean fat oxidation by 27% during 120 min moderate-intensity cycling compared to placebo (P = 0.042), and mean carbohydrate oxidation tended to be lower (P = 0.063). Pre-exercise, plasma NEFA (P = 0.034) and glycerol (P = 0.051) concentrations were greater following NZBC intake, although there was no difference between conditions in the exercise-induced increase in plasma NEFA and glycerol concentrations (P > 0.05). Mean fat oxidation during exercise was moderately associated with pre-exercise plasma NEFA concentrations (r = 0.45, P = 0.016). CONCLUSIONS: Intake of NZBC extract for 7 days elevated resting concentrations of plasma NEFA and glycerol, indicative of higher lipolytic rates, and this may underpin the observed increase in fat oxidation during prolonged cycling in endurance-trained females.


Assuntos
Metabolismo dos Lipídeos/efeitos dos fármacos , Condicionamento Físico Humano/métodos , Extratos Vegetais/farmacologia , Ribes/química , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Adulto , Ciclismo/fisiologia , Glicemia/metabolismo , Suplementos Nutricionais , Ácidos Graxos/sangue , Feminino , Glicerol/sangue , Humanos , Oxirredução , Extratos Vegetais/administração & dosagem
10.
Amino Acids ; 50(1): 189-198, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29082444

RESUMO

Taurine can affect the energy system metabolism, specifically the lipid metabolism, since an increase in lipid oxidation may promote carbohydrate savings. We hypothesized that taurine supplementation associated with high-intensity exercise could increase levels of lipolysis, benefiting swimmer performance. Nine male competitive swimmers performed two 400-m front crawl maximal efforts with a 1-week washout, and the athletes received 6 g of taurine (TAU) or placebo (PLA) supplementation 120 min before performing the effort. Oxygen consumption and the contribution of the energy systems were analyzed post effort using a Quark CPET gas analyzer. Blood samples were collected before, and 5 min post the effort for taurine and glycerol analysis. Immediately before and 3, 5, and 7 min post the effort, blood samples from the earlobe were collected to determine lactate levels. An increase of 159% was observed in taurine plasma levels 120 min post ingestion. Glycerol levels were higher in both groups post effort; however, the TAU condition promoted an 8% higher increase than the PLA. No changes were observed in swimmer performance or lactate levels; however, the percentage change in lactate levels (∆[La-]) was different (TAU: 9.36 ± 2.78 mmol L-1; PLA: 11.52 ± 2.19 mmol L-1, p = 0.04). Acute taurine supplementation 120 min before performing a maximal effort did not improve swimmer performance; however, it increased glycerol plasma levels and reduced both the ∆[La-] and lactic anaerobic system contribution.


Assuntos
Suplementos Nutricionais , Metabolismo Energético/efeitos dos fármacos , Lipólise/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Resistência Física/efeitos dos fármacos , Taurina/farmacologia , Adolescente , Atletas , Exercício Físico , Glicerol/sangue , Humanos , Ácido Láctico/sangue , Masculino , Taurina/sangue , Taurina/metabolismo , Adulto Jovem
11.
Eur J Nutr ; 57(3): 1215-1224, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28255652

RESUMO

PURPOSE: Glycerol usage is increasing in food industry for human and animal nutrition. This study analyzed the impact of glycerol metabolism when orally supplemented during the early stage of rat liver carcinogenesis. METHODS: Wistar rats were subjected to a 2-phase model of hepatocarcinogenesis (initiated-promoted, IP group). IP animals also received glycerol by gavage (200 mg/kg body weight, IPGly group). RESULTS: Glycerol treatment reduced the volume of preneoplastic lesions by decreasing the proliferative status of liver foci, increasing the expression of p53 and p21 proteins and reducing the expression of cyclin D1 and cyclin-dependent kinase 1. Besides, apoptosis was enhanced in IPGly animals, given by an increment of Bax/Bcl-2 ratio, Bad and PUMA mitochondrial expression, a concomitant increase in cytochrome c release and caspase-3 activation. Furthermore, hepatic levels of glycerol phosphate and markers of oxidative stress were increased in IPGly rats. Oxidative stress intermediates act as intracellular messengers, inducing p53 activation and changes in JNK and Erk signaling pathways, with JNK activation and Erk inhibition. CONCLUSION: The present work provides novel data concerning the preventive actions of glycerol during the development of liver cancer and represents an economically feasible intervention to treat high-risk individuals.


Assuntos
Anticarcinógenos/uso terapêutico , Apoptose , Suplementos Nutricionais , Glicerol/uso terapêutico , Neoplasias Hepáticas Experimentais/prevenção & controle , Estresse Oxidativo , Lesões Pré-Cancerosas/prevenção & controle , Animais , Anticarcinógenos/sangue , Anticarcinógenos/metabolismo , Biomarcadores/sangue , Carcinogênese , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Glicerol/sangue , Glicerol/metabolismo , Peroxidação de Lipídeos , Fígado/enzimologia , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas Experimentais/sangue , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/patologia , Sistema de Sinalização das MAP Quinases , Masculino , Mitocôndrias Hepáticas/enzimologia , Mitocôndrias Hepáticas/metabolismo , Mitocôndrias Hepáticas/patologia , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Fosforilação , Lesões Pré-Cancerosas/sangue , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia , Ratos Wistar , Carga Tumoral
12.
Acta Biochim Pol ; 64(4): 687-691, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29202488

RESUMO

PURPOSE: Tadalafil, the phosphodiesterase type 5 inhibitor (PDE5I), has been shown to reduce visceral adipose tissue in rabbit and to improve lean mass content in non-obese men. In order to clarify this effect in humans, in the present study we determined the impact of an acute oral tadalafil administration on lipolysis by evaluating plasma free fatty acids (FFAs) and glycerol. FFAs are potential modulator of inflammation response that we evaluated through tumor necrosis factor alpha (TNFα), interleukin 6 (IL6), interleukin 8 (IL8) and interleukin 10 (IL10) plasma levels. Moreover, we determined whether the effects of tadalafil would be reflected in variation of plasma levels of cGMP and NO, two important molecules involved in PDE5Is signaling. METHODS: Twelve healthy subjects were supplemented with 20 mg of tadalafil or a placebo, in a double-blind, randomized, cross-over design. Blood samples were collected immediately before, and at 2, 6, and 24 hours post ingestion, and assayed for biochemical analysis. RESULTS: A condition effect was noted for FFAs and glycerol, with values higher for tadalafil when compared to the placebo group, at 2 and 6 hours post ingestion. No statistically significant effects were noted for glucose, cGMP, nitrate and nitrite. No inflammatory response was induced by tadalafil. CONCLUSION: Tadalafil, in human subjects, increases lipolysis as evidenced by a significant increase in circulating FFAs and glycerol, without affecting the plasma cGMP and NO levels; noticeably, the increase in FFAs did not develop an inflammatory response. Further well-controlled studies are warranted to assess the impact of tadalafil administration on weight/fat loss.


Assuntos
Ácidos Graxos/sangue , Inflamação/sangue , Inibidores da Fosfodiesterase 5/administração & dosagem , Tadalafila/administração & dosagem , Adulto , Glicemia/metabolismo , GMP Cíclico/sangue , Método Duplo-Cego , Glicerol/sangue , Humanos , Interleucina-6/sangue , Interleucina-8/sangue , Masculino , Óxido Nítrico/sangue , Fator de Necrose Tumoral alfa/sangue
13.
J Int Soc Sports Nutr ; 14: 34, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28919843

RESUMO

BACKGROUND: When combined with exercise, dietary amino acid (AA) supplementation is an effective method for accelerating fat mobilization. However, the effects of single AAs combined with exercise on fat oxidation remains unclear. We hypothesized that consumption of a specific amino acid, L- phenylalanine, may result in the secretion of glucagon, and when combined with exercise may promote fat oxidation. METHODS: Six healthy, active male volunteers were randomized in a crossover study to ingest either phenylalanine (3 g/dose) or placebo. Thirty minutes after ingestion each subject performed workload trials on a cycle ergometer for 1 h at 50% of maximal oxygen consumption. RESULTS: Oral intake of phenylalanine caused a significant increase in the concentrations of plasma glycerol and glucagon during exercise. The respiratory exchange ratio was also decreased significantly following ingestion of phenylalanine. CONCLUSION: These results suggested that pre-exercise supplementation of phenylalanine may stimulate whole body fat oxidation. No serious or study-related adverse events were observed. TRIAL REGISTRATION: UMIN000027502 Registered 26 May 2017. Restrospectively registered.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Exercício Físico/fisiologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Fenilalanina/farmacologia , Adulto , Estudos Cross-Over , Suplementos Nutricionais , Método Duplo-Cego , Glucagon/sangue , Glicerol/sangue , Voluntários Saudáveis , Humanos , Masculino , Oxirredução/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição Esportiva , Adulto Jovem
14.
Mol Genet Metab ; 122(3): 46-53, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28916119

RESUMO

INTRODUCTION: Glycerol phenylbutyrate (GPB) is approved in the US for the management of patients 2months of age and older with urea cycle disorders (UCDs) that cannot be managed with protein restriction and/or amino acid supplementation alone. Limited data exist on the use of nitrogen conjugation agents in very young patients. METHODS: Seventeen patients (15 previously on other nitrogen scavengers) with all types of UCDs aged 2months to 2years were switched to, or started, GPB. Retrospective data up to 12months pre-switch and prospective data during initiation of therapy were used as baseline measures. The primary efficacy endpoint of the integrated analysis was the successful transition to GPB with controlled ammonia (<100µmol/L and no clinical symptoms). Secondary endpoints included glutamine and levels of other amino acids. Safety endpoints included adverse events, hyperammonemic crises (HACs), and growth and development. RESULTS: 82% and 53% of patients completed 3 and 6months of therapy, respectively (mean 8.85months, range 6days-18.4months). Patients transitioned to GPB maintained excellent control of ammonia and glutamine levels. There were 36 HACs in 11 patients before GPB and 11 in 7 patients while on GPB, with a reduction from 2.98 to 0.88 episodes per year. Adverse events occurring in at least 10% of patients while on GPB were neutropenia, vomiting, diarrhea, pyrexia, hypophagia, cough, nasal congestion, rhinorrhea, rash/papule. CONCLUSION: GPB was safe and effective in UCD patients aged 2months to 2years. GPB use was associated with good short- and long-term control of ammonia and glutamine levels, and the annualized frequency of hyperammonemic crises was lower during the study than before the study. There was no evidence for any previously unknown toxicity of GPB.


Assuntos
Amônia/metabolismo , Glutamina/metabolismo , Glicerol/análogos & derivados , Fenilbutiratos/efeitos adversos , Fenilbutiratos/uso terapêutico , Distúrbios Congênitos do Ciclo da Ureia/tratamento farmacológico , Pré-Escolar , Tosse , Gerenciamento Clínico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Febre , Glutamina/efeitos dos fármacos , Glicerol/efeitos adversos , Glicerol/sangue , Glicerol/uso terapêutico , Glicerol/toxicidade , Humanos , Lactente , Masculino , Neutropenia , Fenilbutiratos/sangue , Fenilbutiratos/toxicidade , Estudos Prospectivos , Estudos Retrospectivos
15.
J Am Coll Nutr ; 35(8): 657-669, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27484437

RESUMO

OBJECTIVE: The purpose of this study was to examine the metabolic, lipolytic, and cardiovascular responses to supplementation with p-synephrine alone and in combination with caffeine during resistance exercise (RE). METHODS: Twelve healthy men performed a control RE protocol (6 × 10 repetitions of squats) and were randomly assigned (using a double-blind crossover design with random protocol sequencing) to a supplement sequence: p-synephrine (S; 100 mg), p-synephrine + caffeine (SCF; 100 mg of p-synephrine plus 100 mg of caffeine), or a placebo (P). Subjects reported to the lab at a standard time, consumed a supplement, sat quietly for 45 minutes, performed the RE protocol, and sat quietly for 30 minutes. Blood samples were collected at rest (T1), after sitting quietly for 45 minutes (T2), immediately following RE (T3), and 15 minutes (T4) and 30 minutes (T5) postexercise. Oxygen consumption (VO2) and heart rate (HR) data were collected throughout. RESULTS: Serum glycerol was significantly elevated at T2 only in S and SCF and T3 to T5 in all treatments. Nonesterified fatty acid (NEFA) concentrations did not differ between treatments. Plasma glucose was significantly elevated compared to T1 with highest area under the curve values seen in SCF. Mean VO2 and energy expenditure (EE) were significantly higher in S and SCF through 30 minutes postexercise. Fat oxidation rates favored S and SCF between 25 and 30 minutes postexercise. Mean HR during RE was significantly highest in SCF. CONCLUSIONS: Supplementation with S and SCF increases lipolysis primarily at rest and increases VO2, EE, and fat oxidation rates 30 minutes following RE. No HR changes were observed unless caffeine was added.


Assuntos
Cafeína/administração & dosagem , Sistema Cardiovascular/efeitos dos fármacos , Exercício Físico/fisiologia , Treinamento Resistido , Sinefrina/administração & dosagem , Adulto , Glicemia/análise , Estudos Cross-Over , Suplementos Nutricionais , Método Duplo-Cego , Metabolismo Energético/efeitos dos fármacos , Ácidos Graxos não Esterificados/sangue , Glicerol/sangue , Frequência Cardíaca/efeitos dos fármacos , Humanos , Lipólise/efeitos dos fármacos , Masculino , Metabolismo/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos
16.
PLoS One ; 11(4): e0153229, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27078151

RESUMO

Intake of protein immediately after exercise stimulates protein synthesis but improved recovery of performance is not consistently observed. The primary aim of the present study was to compare performance 18 h after exhaustive cycling in a randomized diet-controlled study (175 kJ·kg(-1) during 18 h) when subjects were supplemented with protein plus carbohydrate or carbohydrate only in a 2-h window starting immediately after exhaustive cycling. The second aim was to investigate the effect of no nutrition during the first 2 h and low total energy intake (113 kJ·kg(-1) during 18 h) on performance when protein intake was similar. Eight endurance-trained subjects cycled at 237±6 Watt (~72% VO2max) until exhaustion (TTE) on three occasions, and supplemented with 1.2 g carbohydrate·kg(-1)·h(-1) (CHO), 0.8 g carbohydrate + 0.4 g protein·kg(-1)·h(-1) (CHO+PRO) or placebo without energy (PLA). Intake of CHO+PROT increased plasma glucose, insulin, and branch chained amino acids, whereas CHO only increased glucose and insulin. Eighteen hours later, subjects performed another TTE at 237±6 Watt. TTE was increased after intake of CHO+PROT compared to CHO (63.5±4.4 vs 49.8±5.4 min; p<0.05). PLA reduced TTE to 42.8±5.1 min (p<0.05 vs CHO). Nitrogen balance was positive in CHO+PROT, and negative in CHO and PLA. In conclusion, performance was higher 18 h after exhaustive cycling with intake of CHO+PROT compared to an isocaloric amount of carbohydrate during the first 2 h post exercise. Intake of a similar amount of protein but less carbohydrate during the 18 h recovery period reduced performance.


Assuntos
Desempenho Atlético/fisiologia , Ciclismo/fisiologia , Carboidratos da Dieta/farmacologia , Proteínas Alimentares/farmacologia , Resistência Física/efeitos dos fármacos , Aminoácidos/sangue , Análise de Variância , Glicemia/metabolismo , Creatina Quinase/sangue , Carboidratos da Dieta/administração & dosagem , Proteínas Alimentares/administração & dosagem , Método Duplo-Cego , Teste de Esforço , Ácidos Graxos não Esterificados/sangue , Glucagon/sangue , Glicerol/sangue , Humanos , Insulina/sangue , L-Lactato Desidrogenase/sangue , Masculino , Mioglobina/sangue , Consumo de Oxigênio/efeitos dos fármacos , Consumo de Oxigênio/fisiologia , Resistência Física/fisiologia , Fatores de Tempo , Adulto Jovem
17.
J Physiol Biochem ; 71(4): 733-42, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26424736

RESUMO

To explore the effects of rutin and exercise on high-fat diet (HFD)-induced disrupted lipolytic signaling, adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling, transient receptor potential cation channel subfamily V member 4 (TRPV4) and its associated protein expression, and whether depot-specific effects existed. C57BL/6J mice were randomized into five groups: chow group, HFD, HFD plus rutin intervention group (HR), HFD combined with treadmill running group (HE), and HFD combined with treadmill running and rutin intervention group (HRE). At the end of the 16-week intervention, lipolytic markers, AMPK signaling pathways, TRPV4, and peroxisome proliferator-activated receptor gamma coactivator 1α + ß (PGC-1α + ß) from adipose tissue were measured by western blotting. In epididymal adipose tissue, HFD resulted in significant reduction in the phosphorylation of hormone sensitive lipase at serine660 (p-HSL660), perilipin A, phosphoenolpyruvate carboxykinase (PEPCK), p-AMPK, and p-acetyl-CoA carboxylase (ACC) protein expression. Exercise intervention and exercise plus rutin completely restored p-HSL660, perilipin A, PEPCK, p-AMPK, and p-ACC protein expression to normal level. HFD and HR groups have reduced expression of PGC-1α + ß, exercise, and exercise plus rutin completely restored PGC-1α + ß expression to normal level. In subcutaneous adipose tissue, HFD elevated TRPV4, exercise, and exercise plus rutin completely reduced TRPV4 to normal level. HR, HE, and HRE group have increased PGC-1α + ß. In conclusion, depot-specific effects existed in regards to how rutin and exercise affect lipolytic signaling and p-AMPK, as well as TRPV4 and PGC-1α + ß expression.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Gordura Intra-Abdominal/metabolismo , Lipólise , Obesidade/metabolismo , Rutina/uso terapêutico , Canais de Cátion TRPV/metabolismo , Animais , Fármacos Antiobesidade/farmacologia , Terapia Combinada , Dieta Hiperlipídica/efeitos adversos , Avaliação Pré-Clínica de Medicamentos , Epididimo/metabolismo , Terapia por Exercício , Ácidos Graxos não Esterificados/sangue , Expressão Gênica , Glicerol/sangue , Masculino , Camundongos Endogâmicos C57BL , Obesidade/terapia , Corrida , Rutina/farmacologia , Transdução de Sinais , Canais de Cátion TRPV/genética , Fatores de Transcrição/metabolismo
18.
Molecules ; 20(6): 10047-64, 2015 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-26035102

RESUMO

Corydalis Rhizoma, named YuanHu in China, is the dried tuber of Corydalis yanhusuo W.T. Wang which is used in Traditional Chinese Medicine for pain relief and blood activation. Previous pharmacological studies showed that apart from analgesics, the alkaloids from YuanHu may be useful in the therapy of depression by acting on the GABA, dopamine and benzodiazepine receptors. In this study, the antidepressive effect of the total alkaloid of YuanHu (YHTA) was investigated in a chronic unpredictable mild stress (CUMS) rat model using 1H-NMR-based metabonomics. Plasma metabolic profiles were analyzed and multivariate data analysis was applied to discover the metabolic biomarkers in CUMS rats. Thirteen biomarkers of CUMS-introduced depression were identified, which are myo-inositol, glycerol, glycine, creatine, glutamine, glutamate, ß-glucose, α-glucose, acetoacetate, 3-hydroxybutyrate, leucine and unsaturated lipids (L7, L9). Moreover, a metabolic network of the potential biomarkers in plasma perturbed by CUMS was detected. After YHTA treatment, clear separation between the model group and YHTA-treated group was achieved. The levels of all the abnormal metabolites mentioned above showed a tendency of restoration to normal levels. The results demonstrated the therapeutic efficacy of YHTA against depression and suggested that NMR-based metabolomics can provide a simple and easy tool for the evaluation of herbal therapeutics.


Assuntos
Alcaloides/farmacologia , Antidepressivos/farmacologia , Corydalis/química , Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Estresse Psicológico/tratamento farmacológico , Alcaloides/isolamento & purificação , Aminoácidos/sangue , Animais , Antidepressivos/isolamento & purificação , Biomarcadores/sangue , Glicemia/metabolismo , Depressão/fisiopatologia , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/isolamento & purificação , Ácidos Graxos Insaturados/sangue , Glicerol/sangue , Inositol/sangue , Metabolômica , Espectroscopia de Prótons por Ressonância Magnética , Ratos , Ratos Sprague-Dawley , Rizoma/química , Estresse Psicológico/fisiopatologia
19.
Pancreatology ; 15(4): 337-43, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26048200

RESUMO

BACKGROUND AND OBJECTIVES: Chinese herbal drug Da-Cheng-Qi decoction (DCQD) has been widely used for decades to treat acute pancreatitis (AP). Previous trials are mostly designed to state the potential mechanisms of the therapeutic effects rather than to detect its whole effect on metabolism. This study aimed to investigate the efficacy of DCQD on metabolism in AP. METHODS: Twenty-two male adult Sprague-Dawley rats were randomized into three groups. AP was induced by retrograde ductal infusion of 3.5% sodium taurocholate solution in DCQD and AP group, while 0.9% saline solution was used in sham operation (SO) group. Blood samples were obtained 12 h after drug administration and a 600 MHz superconducting Nuclear Magnetic Resonance (NMR) spectrometer was used to detected plasma metabolites. Principal Components Analysis (PCA) and Partial Least Squares-Discriminant Analysis after Orthogonal Signal Correction (OSC-PLS-DA) were applied to analyze the Longitudinal Eddy-delay (LED) and Carr-Purcell-Meiboom-Gill (CPMG) spectra. RESULTS: Differences in concentrations of metabolites among the three groups were detected by OSC-PLS-DA of 1HNMR spectra (both LED and CPMG). Compared with SO group, DCQD group had higher levels of plasma glycerol, glutamic acid, low density lipoprotein (LDL), saturated fatty acid (FA) and lower levels of alanine and glutamine, while the metabolic changes were reversed in the AP group. CONCLUSIONS: Our results demonstrated that DCQD was capable of altering the changed concentrations of metabolites in rats with AP and 1HNMR-based metabolomic approach provided a new methodological cue for systematically investigating the efficacies and mechanisms of DCQD in treating AP.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/uso terapêutico , Pancreatite/tratamento farmacológico , Pancreatite/metabolismo , Alanina/sangue , Animais , Biotransformação , LDL-Colesterol/sangue , Ácidos Graxos/sangue , Ácido Glutâmico/sangue , Glutamina/sangue , Glicerol/sangue , Espectroscopia de Ressonância Magnética , Masculino , Metabolômica , Ratos , Ratos Sprague-Dawley
20.
Nutrition ; 30(7-8 Suppl): S17-20, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24985100

RESUMO

OBJECTIVE: Botanical compounds and extracts are widely used as nutritional supplements for the promotion of health or the prevention of disease. An extract of Artemisia dracunculus (PMI 5011) has been shown to improve insulin action, yet the precise mechanism is not known. The aim of this study is to demonstrate that the mechanism by which PMI 5011 and two related Artemisia extracts improve insulin action is associated with a down-regulation of de novo lipogenesis (DNL) in the liver and an increase in DNL in the adipose tissue. METHODS: Diet-induced obese 16-wk-old male mice (C57 BL/6 J) were divided into four groups: (control, 5011, Santa, and Scopa) and fed for 30 d with respective extracts incorporated into the diet at 1% (w/w). Deuterium was administered on day 30 for the measurement of DNL in blood, liver, and white adipose tissue. Individual fatty acids and glycerol levels were also measured. RESULTS: No statistically significant differences were seen in DNL between the control group and the three botanical treatments. Plasma levels of all four long-chain fatty acids were significantly lower in the three treatment groups. Glycerol in the plasma was lower in the treatment groups compared with the control group; however, this did not reach statistical significance in all cases. Tissue levels of the fatty acids and glycerol did not differ between any of the treatment groups. CONCLUSIONS: These results suggest that botanicals may not affect fractional DNL in animals on a high-fat diet. However, there were decreases in long-chain fatty acids and in glycerol coming from the newly synthesized triglycerides in plasma.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Artemisia , Insulina/metabolismo , Lipogênese/efeitos dos fármacos , Fígado/efeitos dos fármacos , Obesidade/metabolismo , Extratos Vegetais/farmacologia , Tecido Adiposo/metabolismo , Animais , Dieta Hiperlipídica , Gorduras na Dieta/administração & dosagem , Ácidos Graxos/sangue , Ácidos Graxos/metabolismo , Glicerol/sangue , Glicerol/metabolismo , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/etiologia , Triglicerídeos/biossíntese , Triglicerídeos/sangue
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