RESUMEN
This study tested the hypothesis that elevated L-leucine concentrations in plasma reduce nitric oxide (NO) synthesis by endothelial cells (ECs) and affect adiposity in obese rats. Beginning at four weeks of age, male Sprague-Dawley rats were fed a casein-based low-fat (LF) or high-fat (HF) diet for 15 weeks. Thereafter, rats in the LF and HF groups were assigned randomly into one of two subgroups (n = 8/subgroup) and received drinking water containing either 1.02% L-alanine (isonitrogenous control) or 1.5% L-leucine for 12 weeks. The energy expenditure of the rats was determined at weeks 0, 6, and 11 of the supplementation period. At the end of the study, an oral glucose tolerance test was performed on all the rats immediately before being euthanized for the collection of tissues. HF feeding reduced (P < 0.001) NO synthesis in ECs by 21% and whole-body insulin sensitivity by 19% but increased (P < 0.001) glutamine:fructose-6-phosphate transaminase (GFAT) activity in ECs by 42%. Oral administration of L-leucine decreased (P < 0.05) NO synthesis in ECs by 14%, increased (P < 0.05) GFAT activity in ECs by 35%, and reduced (P < 0.05) whole-body insulin sensitivity by 14% in rats fed the LF diet but had no effect (P > 0.05) on these variables in rats fed the HF diet. L-Leucine supplementation did not affect (P > 0.05) weight gain, tissue masses (including white adipose tissue, brown adipose tissue, and skeletal muscle), or antioxidative capacity (indicated by ratios of glutathione/glutathione disulfide) in LF- or HF-fed rats and did not worsen (P > 0.05) adiposity, whole-body insulin sensitivity, or metabolic profiles in the plasma of obese rats. These results indicate that high concentrations of L-leucine promote glucosamine synthesis and impair NO production by ECs, possibly contributing to an increased risk of cardiovascular disease in diet-induced obese rats.
Asunto(s)
Resistencia a la Insulina , Ratas , Masculino , Animales , Leucina/farmacología , Óxido Nítrico , Ratas Sprague-Dawley , Células Endoteliales/metabolismo , Obesidad/metabolismo , Dieta Alta en Grasa/efectos adversos , Suplementos DietéticosRESUMEN
OBJECTIVE: Since we and others have shown that supplemental magnesium raises whole blood ionized magnesium (iMg2+) we investigated the relationships between self-reported dietary magnesium intake and concentrations of whole blood iMg2+ and serum magnesium (s-Mg). METHODS: We obtained whole blood iMg2+ concentrations, as well as s-Mg concentrations, from a pilot, three-arm, randomized, controlled, crossover bioavailability study of magnesium supplements (n = 23; 105 measures). Dietary magnesium intake was assessed using three-day food records and the Nutrition Data System for Research (NDSR, University of Minnesota, MN, USA). Whole blood iMg2+ was measured with an electrode analyser (NOVA Biochemical, Waltham, MA, USA), whereas s-Mg was measured using atomic absorption spectroscopy. A linear mixed-effects model was employed with dietary magnesium as the outcome variable and iMg2+, s-Mg, study treatment and study visit as fixed effects. We adjusted age, gender, race and body mass index covariates. RESULTS: Values for dietary magnesium, iMg2+ and s-Mg were 303.8 ± 118.9 mg/day, 1.3 ± 0.1 mg/dL and 2.2 ± 4.1 mg/dL, respectively. No association was found between dietary magnesium intake and iMg2+ -125 ± 176.95 (p = .49) or s-Mg -9.33 ± 5.04 (p = .08). CONCLUSIONS: Whole blood iMg2+ and s-Mg concentrations do not reflect short-term self-reported dietary intake in adults. Further research is needed to determine whether blood biomarkers of magnesium may reflect dietary magnesium intake.Key messagesDietary intake of magnesium, a shortfall nutrient, may be objectively measured using blood biomarkers of magnesium.Serum magnesium and whole blood iMg2+ were not associated with short-term dietary intake of magnesium.
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Magnesio , Estado Nutricional , Adulto , Humanos , AutoinformeRESUMEN
Previous studies with animals and humans have shown beneficial effects of dietary supplementation with L-arginine (Arg) on reducing white fat and improving health. At present, a long-term safe level of Arg administration to adult humans is unknown. The objective of this study was to conduct a randomized, placebo-controlled, clinical trial to evaluate the safety and tolerability of oral Arg in overweight or obese but otherwise healthy adults with a body mass index of ≥ 25 kg/m2. A total of 142 subjects completed a 7-day wash-in period using a 12 g Arg/day dose. All the remaining eligible 101 subjects who tolerated the wash-in dose (45 men and 56 women) were assigned randomly to ingest 0, 15 or 30 g Arg (as pharmaceutical-grade Arg-HCl) per day for 90 days. Arg was taken daily in at least two divided doses by mixing with a flavored beverage. At Days 0 and 90, blood pressures of study subjects were recorded, their physical examinations were performed, and their blood and 24-h urine samples were obtained to measure: (1) serum concentrations of amino acids, glucose, fatty acids, and related metabolites; and (2) renal, hepatic, endocrine and metabolic parameters. Our results indicate that the serum concentration of Arg in men or women increased (P < 0.05) progressively with increasing oral Arg doses from 0 to 30 g/day. Dietary supplementation with 30 g Arg/day reduced (P < 0.05) systolic blood pressure and serum glucose concentration in females, as well as serum concentrations of free fatty acids in both males and females. Based on physiological and biochemical variables, study subjects tolerated oral administration of 15 and 30 g Arg/day without adverse events. We conclude that a long-term safe level of dietary Arg supplementation is at least 30 g/day in adult humans.
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Arginina/administración & dosificación , Suplementos Dietéticos/análisis , Adulto , Aminoácidos/sangre , Arginina/efectos adversos , Arginina/sangre , Presión Sanguínea/efectos de los fármacos , Suplementos Dietéticos/efectos adversos , Ácidos Grasos/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Male Zucker diabetic fatty (ZDF) rats were used to study effects of oral administration of interferon tau (IFNT) in reducing obesity. Eighteen ZDF rats (28 days of age) were assigned randomly to receive 0, 4, or 8 µg IFNT/kg body weight (BW) per day (n = 6/group) for 8 weeks. Water consumption was measured every two days. Food intake and BW were recorded weekly. Energy expenditure in 4-, 6-, 8-, and 10-week-old rats was determined using indirect calorimetry. Starting at 7 weeks of age, urinary glucose, and ketone bodies were tested daily. Rates of glucose and oleate oxidation in liver, brown adipose tissue, and abdominal adipose tissue, as well as leucine catabolism in skeletal muscle, and lipolysis in white and brown adipose tissues were greater for rats treated with 8 µg IFNT/kg BW/day in comparison with control rats. Treatment with 8 µg IFNT/kg BW/day increased heat production, reduced BW gain and adiposity, ameliorated fatty liver syndrome, delayed the onset of diabetes, and decreased concentrations of glucose, free fatty acids, triacylglycerol, cholesterol, and branched-chain amino acids in plasma, compared with control rats. Oral administration of 8 µg IFNT/kg BW/day ameliorated oxidative stress in skeletal muscle, liver, and adipose tissue, as indicated by decreased ratios of oxidized glutathione to reduced glutathione and increased concentrations of tetrahydrobiopterin. These results indicate that IFNT stimulates oxidation of energy substrates and reduces obesity in ZDF rats and may have broad important implications for preventing and treating obesity-related diseases in mammals.
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Adiposidad/efectos de los fármacos , Fármacos Antiobesidad/administración & dosificación , Diabetes Mellitus Tipo 2/prevención & control , Interferón Tipo I/administración & dosificación , Obesidad/tratamiento farmacológico , Proteínas Gestacionales/administración & dosificación , Adiponectina/sangre , Tejido Adiposo Blanco/efectos de los fármacos , Tejido Adiposo Blanco/patología , Administración Oral , Aminoácidos/sangre , Animales , Glucemia , Diabetes Mellitus Tipo 2/sangre , Evaluación Preclínica de Medicamentos , Metabolismo Energético/efectos de los fármacos , Glicerol/metabolismo , Insulina/sangre , Leptina/sangre , Leucina Transaminasa/metabolismo , Lípidos/sangre , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Obesidad/sangre , Obesidad/patología , Tamaño de los Órganos , Oxidación-Reducción , Estrés Oxidativo , Ratas , Ratas ZuckerRESUMEN
Dietary intake of glutamate by postweaning pigs is markedly reduced due to low feed consumption. This study was conducted to determine the safety and efficacy of dietary supplementation with monosodium glutamate (MSG) in postweaning pigs. Piglets were weaned at 21 days of age to a corn and soybean meal-based diet supplemented with 0, 0.5, 1, 2, and 4 % MSG (n = 25/group). MSG was added to the basal diet at the expense of cornstarch. At 42 days of age (21 days after weaning), blood samples (10 mL) were obtained from the jugular vein of 25 pigs/group at 1 and 4 h after feeding for hematological and clinical chemistry tests; thereafter, pigs (n = 6/group) were euthanized to obtain tissues for histopathological examinations. Feed intake was not affected by dietary supplementation with 0-2 % MSG and was 15 % lower in pigs supplemented with 4 % MSG compared with the 0 % MSG group. Compared with the control, dietary supplementation with 1, 2 and 4 % MSG dose-dependently increased plasma concentrations of glutamate, glutamine, and other amino acids (including lysine, methionine, phenylalanine and leucine), daily weight gain, and feed efficiency in postweaning pigs. At day 7 postweaning, dietary supplementation with 1-4 % MSG also increased jejunal villus height, DNA content, and antioxidative capacity. The MSG supplementation dose-dependently reduced the incidence of diarrhea during the first week after weaning. All variables in standard hematology and clinical chemistry tests, as well as gross and microscopic structures, did not differ among the five groups of pigs. These results indicate that dietary supplementation with up to 4 % MSG is safe and improves growth performance in postweaning pigs.
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Alimentación Animal/análisis , Suplementos Dietéticos/análisis , Glutamato de Sodio/metabolismo , Porcinos/crecimiento & desarrollo , Animales , Femenino , Ácido Glutámico/sangre , Glutamina/sangre , Masculino , Glutamato de Sodio/efectos adversos , Porcinos/genética , Porcinos/metabolismo , DesteteRESUMEN
As the nitrogenous precursor of nitric oxide, L-arginine regulates multiple metabolic pathways involved in the metabolism of fatty acids, glucose, amino acids, and proteins through cell signaling and gene expression. Specifically, arginine stimulates lipolysis and the expression of key genes responsible for activation of fatty acid oxidation to CO2 and water. The underlying mechanisms involve increases in the expression of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha), mitochondrial biogenesis, and the growth of brown adipose tissue growth. Furthermore, arginine regulates adipocyte-muscle crosstalk and energy partitioning via the secretion of cytokines and hormones. In addition, arginine enhances AMP-activated protein kinase (AMPK) expression and activity, thereby modulating lipid metabolism and energy balance toward the loss of triacylglycerols. Growing evidence shows that dietary supplementation with arginine effectively reduces white adipose tissue in Zucker diabetic fatty rats, diet-induced obese rats, growing-finishing pigs, and obese patients with type II diabetes. Thus, arginine can be used to prevent and treat adiposity and the associated metabolic syndrome.