RESUMEN
BACKGROUND: It has been established in RCTs that high dose of phytosterols can significantly reduce blood cholesterol. However, it was uncertain whether low dose of phytosterols from daily diets was effective. In this study, we evaluated the associations between dietary phytosterols and body mass index (BMI), waist circumference (WC), blood glucose, serum lipid profiles and prevalence of overweight/obesity and abdominal obesity in healthy subjects. METHODS: Four hundred nine men and 503 women aged 18-60 years were included in this study. Dietary intakes of phytosterols were estimated using a validated food frequency questionnaire. Height, body weight, WC and blood pressure were measured, an oral glucose tolerance test was performed. Moreover, fasting serum triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDLc) and low density lipoprotein cholesterol (LDLc) were further determined. RESULTS: When comparing extreme quartiles of dietary phytosterols, significant differences of BMI, WC, systolic blood pressure (SBP), diastolic blood pressure (DBP), serum TC and LDLc were found. Dietary phytosterols presented a negative association with BMI, WC, SBP, DBP, serum TC and LDLc (with and without adjustment for energy). After adjustment for confounders, we found higher dietary phytosterols were linked with lower prevalence of overweight/obesity (OR highest vs. lowest quartile = 0.487; 95% CI 0.234, 0.918 for men; OR highest vs. lowest quartile = 0.277; 95% CI 0.124, 0.619 for women) and abdominal obesity (OR highest vs. lowest quartile = 0.344; 95% CI 0.144, 0.819 for men; OR highest vs. lowest quartile = 0.321; 95% CI 0.140, 0.571 for women). CONCLUSIONS: Higher dietary phytosterols were associated with lower BMI, WC, blood pressure, serum TC and LDLc and lower prevalence of overweight/obesity and abdominal obesity in Chinese adults.
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LDL-Colesterol/sangre , Lípidos/sangre , Obesidad/sangre , Fitosteroles/administración & dosificación , Adolescente , Adulto , Glucemia , Presión Sanguínea , Índice de Masa Corporal , China/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad/dietoterapia , Obesidad/epidemiología , Sobrepeso , Encuestas y Cuestionarios , Triglicéridos/sangre , Circunferencia de la Cintura , Adulto JovenRESUMEN
BACKGROUND/AIMS: Elevation of plasma sulfur-containing amino acids (SAAs) is generally associated with higher body mass index (BMI) and unfavorable lipid profiles. It is not known how dietary SAAs relate to these associations in humans. METHODS: A convenient tool named internet-based dietary questionnaire for Chinese (IDQC) was used to estimate dietary SAAs intake. A total of 936 participants were randomly recruited and asked to complete the IDQC. Furthermore, 90 subjects were randomly selected to perform a subgroup study. The associations between dietary SAAs and prevalence of obesity, lipid profiles, and status of insulin resistance (IR), inflammation and oxidative stress were assessed. RESULTS: Dietary total SAAs and cysteine of overweight/obese participants were significantly higher. Dietary total SAAs and cysteine were positively associated with BMI and waist circumference. Higher dietary total SAAs were associated with higher prevalence of overweight/obesity. Higher dietary total SAAs and cysteine also associated with higher serum triglyceride (total cholesterol), low density lipoprotein, fasting blood glucose, 2 h-postprandial glucose, and homeostasis model assessment of IR. In the subgroup study, positive associations between dietary SAAs and inflammation biomarkers were also observed. CONCLUSIONS: Dietary SAAs are associated with higher prevalence of overweight/obesity, unfavorable lipid profiles and status of IR, and inflammation.
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Aminoácidos/química , Dieta , Obesidad/epidemiología , Sobrepeso/epidemiología , Azufre/administración & dosificación , Adolescente , Adulto , Pueblo Asiatico , Glucemia , Índice de Masa Corporal , China , Estudios Transversales , Cisteína/administración & dosificación , Femenino , Humanos , Inflamación , Internet , Lípidos/sangre , Masculino , Estrés Oxidativo , Prevalencia , Encuestas y Cuestionarios , Circunferencia de la Cintura , Adulto JovenRESUMEN
Whether supplementation of curcuminoids decreases serum adipocyte-fatty acid binding protein (A-FABP) level and whether this decrease benefits glucose control is unclear. One-hundred participants (n=50 administered curcuminoids, n=50 administered placebo) from our previous report on the effect of curcuminoids on type 2 diabetes in a 3-month intervention were assessed for levels of serum A-FABP, oxidative stress, and inflammatory biomarkers. Curcuminoids supplementation led to significant decreases in serum A-FABP, C-reactive protein (CRP), tumor necrosis factor-α, and interleukin-6 levels. Curcuminoids supplementation also significantly increased serum superoxide dismutase (SOD) activity. The change in serum A-FABP levels showed positive correlations with changes in levels of glucose, free fatty acids (FFAs), and CRP in subjects supplemented with curcuminoids. Further stepwise regression analysis showed that A-FABP was an independent predictor for levels of FFAs, SOD, and CRP. These results suggest that curcuminoids may exert anti-diabetic effects, at least in part, by reductions in serum A-FABP level. A-FABP reduction is associated with improved metabolic parameters in human type 2 diabetes.
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Glucemia/análisis , Curcumina/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Proteínas de Unión a Ácidos Grasos/sangre , Hipoglucemiantes/uso terapéutico , Biomarcadores/sangre , Curcumina/administración & dosificación , Curcumina/farmacología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/inmunología , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/farmacología , Obesidad/sangre , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Obesidad/inmunología , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/inmunología , Resultado del TratamientoRESUMEN
OBJECTIVE: Study the effects of ß-glucan in highland barley on blood glucose and serum lipid in high fat diet induced C57 mouse. METHODS: Using table of random number, 40 male C57BL/6 mice were randomly divided into 4 groups (10 mice in each group) by weight: high dosage group (4% ß-glucan and high fat diet), low dosage group (2% ß-glucan and high fat diet), high fat diet group and normal control group. Food-intake and body weight of C57 mouse were observed. Glucose tolerance tests and examinations of fasting blood glucose were performed at the end of 11 weeks of intervention. Mice were sacrificed after 12 wk of treatment, and serum specimens were obtained to test relevant biochemical indicators. RESULTS: After 12 weeks raise, among high dosage group, low dosage group, high fat diet group and normal control group, the weight was (32.8 ± 1.5), (40.4 ± 1.9), (40.7 ± 2.1) and (33.5 ± 1.3) g, respectively (F = 55.26, P < 0.05); average food intake was (3.48 ± 0.56), (3.69 ± 0.76), (3.66 ± 0.81) and (3.54 ± 0.61) g/d respectively (F = 0.26, P > 0.05); fasting blood-glucose was (5.29 ± 1.59), (6.13 ± 1.75), (7.63 ± 1.09) and (4.24 ± 0.98) mmol/L respectively (F = 9.54, P < 0.01); serum insulin level was (1.97 ± 0.10), (2.44 ± 0.24), (3.02 ± 0.36) and (1.48 ± 0.28) ng/ml respectively (F = 47.58, P < 0.01); the area under blood glucose concentration curve was (25.81 ± 1.44), (30.42 ± 2.01), (35.17 ± 1.20) and (21.03 ± 1.24) mmol×L(-1)×h(-1), respectively (F = 64.98, P < 0.05); insulin resistance index was (9.84 ± 3.78), (13.69 ± 4.48), (21.54 ± 3.27) and (5.81 ± 1.59) respectively (F = 30.18, P < 0.01); serum total cholesterol (TC) level was (4.05 ± 0.88), (4.30 ± 0.48), (4.73 ± 0.66) and (3.37 ± 0.40) mmol/L respectively (F = 6.70, P < 0.01); serum triglyceride (TG) level was (0.90 ± 0.09), (0.98 ± 0.09), (1.05 ± 0.06) and (0.76 ± 0.26) mmol/L respectively (F = 6.75, P < 0.01); serum high-density lipoprotein cholesterol (HDL-C) level was (2.91 ± 0.59), (3.34 ± 0.46), (4.89 ± 0.42) and (3.24 ± 0.37) mmol/L respectively (F = 31.73, P < 0.01); serum low-density lipoprotein cholesterol (LDL-C) level was (0.25 ± 0.15), (0.42 ± 0.19), (0.72 ± 0.12) and (0.32 ± 0.11) mmol/L, respectively (F = 17.27, P < 0.01); free fatty acids (FFA) level was (1.06 ± 0.03), (1.05 ± 0.05), (1.18 ± 0.32) and (1.04 ± 0.02) mmol/L, respectively (F = 1.36, P > 0.05); HDL-C/LDL-C was (13.77 ± 5.51), (9.11 ± 3.53), (7.04 ± 1.65) and (11.21 ± 3.31), respectively (F = 5.24, P < 0.01). CONCLUSION: The ß-glucan in highland barley reduced the serum glucose and serum lipid, as well as insulin resistance and the risk of arterial sclerosis in high-fat induced C57 mouse.
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Dieta Alta en Grasa/efectos adversos , Hordeum , Lípidos/sangre , beta-Glucanos/farmacología , Animales , Glucemia , Colesterol/sangre , LDL-Colesterol/sangre , Prueba de Tolerancia a la Glucosa , Masculino , Ratones , Ratones Endogámicos C57BL , Triglicéridos/sangreRESUMEN
Adipocyte differentiation and adipogenesis are closely related to obesity and obesity-induced metabolic disorders. The calcium-sensing receptor (CaSR) has been reported to play an antilipolytic role in human adipocyte and regulate cell differentiation in many tissues. However, the effects of CaSR on adipocyte differentiation and adipogenesis have not been clarified. In the study, we observed that activation of CaSR significantly promoted adipocyte differentiation and adipogenesis in human SW872 adipocytes. Gene expression analysis revealed that the CaSR activation increased the transcription factor proliferator-activated receptor γ (PPARγ) and its downstream genes including CCAAT element binding protein α (C/EBPα), adipose fatty acid-binding protein (aP2), and lipoprotein lipase. The activity of glycerol-3-phosphate dehydrogenase was also increased after the stimulation of CaSR. In addition, levels of cyclic AMP and calcium which have been shown to regulate PPARγ gene expression were significantly affected by the activation of CaSR. These effects could be suppressed by CaSR small interfering RNA (CaSR-siRNA). In conclusion, our findings suggest that activation of CaSR promotes differentiation and adipogenesis in adipocytes, which might be achieved by upregulating PPARγ and its downstream gene expressions. Therefore, CaSR in adipocytes may be involved in the pathogenesis of obesity by promoting adipocyte differentiation and adipogenesis.
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Adipocitos/fisiología , Adipogénesis , PPAR gamma/metabolismo , Receptores Sensibles al Calcio/metabolismo , Adipocitos/metabolismo , Proteína alfa Potenciadora de Unión a CCAAT/genética , Proteína alfa Potenciadora de Unión a CCAAT/metabolismo , Señalización del Calcio , Diferenciación Celular , Línea Celular , AMP Cíclico/metabolismo , Proteínas de Unión a Ácidos Grasos/genética , Proteínas de Unión a Ácidos Grasos/metabolismo , Gadolinio/farmacología , Expresión Génica , Humanos , Lipoproteína Lipasa/genética , Lipoproteína Lipasa/metabolismo , PPAR gamma/genética , Receptores Sensibles al Calcio/agonistas , Receptores Sensibles al Calcio/genética , Triglicéridos/metabolismoRESUMEN
The aims of the present study were to examine the serum amino acid profiles in obese and non-obese women and investigate the relationships between the serum amino acids and inflammation and oxidative stress in a human case-control study. Serum amino acids, inflammatory biomarkers (C-reactive protein and IL-6) and oxidative biomarkers (superoxide dismutase, malondialdehyde and glutathione peroxidase) were measured and compared in 235 obese women and 217 non-obese controls. The relationships between serum amino acids and inflammatory and oxidative biomarkers were examined using multiple linear regression. Among the amino acids determined, serum histidine, arginine, threonine, glycine, lysine and serine were found to be significantly lower in obese women as compared to non-obese controls (P < 0·001). The difference was the greatest for histidine (P < 0·001). In obese women, both histidine and arginine were negatively associated with inflammation and oxidative stress. In non-obese controls, histidine was negatively associated with oxidative stress. The findings in this study indicate that the metabolism of amino acids is abnormal in obese women in whom histidine and arginine have close relationships with inflammation and oxidative stress.
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Arginina/sangre , Histidina/sangre , Inflamación/metabolismo , Obesidad/metabolismo , Obesidad/patología , Estrés Oxidativo/fisiología , Adulto , Arginina/metabolismo , Biomarcadores , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Femenino , Histidina/metabolismo , Humanos , Interleucina-6/sangre , Modelos Lineales , Persona de Mediana EdadRESUMEN
BACKGROUND: Obesity is closely associated with chronic diseases such as hypertension, type 2 diabetes mellitus (T2DM), and dyslipidemia. We analyzed the optimal obesity index cut-off values for metabolic syndrome (MetS), and identified the obesity index that is more closely associated with these chronic diseases, in a population of northern Chinese. METHODS: We surveyed 8940 adults (age, 20-74 years) living in northern China for chronic diseases. Receiver operating characteristics (ROC) analysis, relative risk, and multivariate regression were used to develop an appropriate index and optimal cut-off values for MetS and obesity-related chronic diseases. RESULTS: Waist circumference (WC) and body mass index (BMI) were good markers for MetS, WC was a good marker for T2DM and dyslipidemia, and BMI was a good marker for hypertension. The optimal BMI cut-off value of MetS was 24 kg/m², and the optimal WC cut-offs were 86 cm and 78 cm in men and women, respectively. Relative risk regression models showed that BMI was associated with hypertension, T2DM, and hypertriglyceridemia and a higher prevalence ratio (PR) for hypertension: 2.35 (95% CI, 2.18-2.50). WC was associated with T2DM, hypertension, and hypertriglyceridemia, with PRs of 2.05 (1.63-2.55) for T2DM and 2.47 (2.04-2.85) for hypertriglyceridemia. In multivariate regression models, the standardized regression coefficients (SRCs) of BMI were greater for SBP and DBP, and the SRC of WC was greater for fasting blood glucose, 2-hour postload blood glucose, triglyceride, and total cholesterol. CONCLUSIONS: Our analysis of a population of northern Chinese indicates that the optimal cut-off values for MetS are WCs of 86 cm in men and 78 cm in women and a BMI of 24 kg/m² in both sexes. BMI was strongly associated with hypertension, while WC was strongly associated with T2DM and dyslipidemia.
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Índice de Masa Corporal , Diabetes Mellitus Tipo 2/epidemiología , Dislipidemias/epidemiología , Hipertensión/epidemiología , Circunferencia de la Cintura , Adulto , Anciano , Antropometría/métodos , China/epidemiología , Femenino , Humanos , Masculino , Síndrome Metabólico/epidemiología , Persona de Mediana Edad , Análisis Multivariante , Obesidad/complicaciones , Curva ROC , Factores de Riesgo , Adulto JovenRESUMEN
To study the toxic effect of chronic exposure to acephate at low-dose levels, a metabolomics approach based on ultra-performance liquid chromatography/mass spectrometry (UPLC-MS) was applied. Three different doses of 0.5 mg/kg/day, 1.5 mg/kg/day, and 4.5 mg/kg/day acephate were administered to Wistar rats for 24 weeks. Endogenous metabolite profiles were obtained with UPLC-MS for all rats at six time points after treatment. Some metabolites like dimethylthiophosphate and uric acid in urine were detected at week 4. Dimethylthiophosphate, which had the most significant elevations compared with other biomarkers, was considered as an early, sensitive biomarker of exposure to acephate. Moreover, there were some endogenous metabolite changes, which demonstrated that the doses of 1.5 mg/kg/day and 4.5 mg/kg/day of acephate led to renal injury and perturbed the normal metabolic processes of rats, including glucose, nucleic acid, and protein metabolism. A connection between exposure to acephate and the metabolic disturbance has been found and interpreted. Our study indicates that the metabolomics approach based on UPLC-MS of urine provides more information on toxicity than the conventional toxicological evaluation methods in measuring changes and can be considered as a promising technique for the study of the toxic effect of acephate.
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Cromatografía Liquida , Contaminantes Ambientales/toxicidad , Espectrometría de Masas , Metabolismo/efectos de los fármacos , Metaboloma/efectos de los fármacos , Compuestos Organotiofosforados/toxicidad , Fosforamidas/toxicidad , Animales , Biomarcadores/análisis , Biomarcadores/orina , Masculino , Metabolómica , Fosfatos/análisis , Fosfatos/orina , Ratas , Ratas WistarRESUMEN
Low-calcium intake is associated with increased risk of obesity, but the mechanism underlying this is not clear. We previously reported that the calcium-sensing receptor (CaSR) plays an important role in modulating the expression of rate-limiting lipolysis enzymes in human adipocytes. In the present study, rats were fed diets containing normal [0.50% (NC)], low [0.30% (LC)], or very low [0.15% (VLC)] calcium for 15 wk. Ten rats of each group were killed at wk 5, 10, and 15 of the intervention. The LC-fed rats had greater visceral fat mass, lower serum FFA and glycerol concentrations, and greater CaSR expression in white adipose tissue than did those fed the NC diet at wk 10 and 15. Hormone-sensitive lipase (HSL) and adipose TG lipase (ATGL) protein levels were lower, whereas fatty acid synthase mRNA in white adipose tissue was greater in the LC-fed rats compared with the NC-fed rats. These differences from the NC group were greater in the VLC group than in the LC group at wk 15. In vitro experiments showed that 1,25-dihydroxycholecalciferol stimulated the expression of CaSR through the nuclear vitamin D receptor (nVDR). This resulted in an antilipolytic effect by increasing intracellular calcium, decreasing the intracellular cAMP level, and downregulating HSL and ATGL protein expression in adipocytes. These effects were suppressed by either nVDR or CaSR small-interfering RNA. These results suggest that CaSR affects fat accumulation by mediating antilipolytic pathways in adipose tissue of rats fed low-calcium diets.
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Calcio de la Dieta/administración & dosificación , Grasa Intraabdominal/fisiología , Lipólisis/fisiología , Receptores Sensibles al Calcio/fisiología , Animales , Secuencia de Bases , Western Blotting , Densidad Ósea , Calcitriol/sangre , Calcio/sangre , AMP Cíclico/metabolismo , Conducta Alimentaria , Grasa Intraabdominal/metabolismo , Lipoproteína Lipasa/sangre , Masculino , Hormona Paratiroidea/sangre , ARN Interferente Pequeño , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Esteroide Hidroxilasas/metabolismo , Aumento de PesoRESUMEN
To select early, sensitive biomarkers of 3-chloro-1,2-propanediol (3-MCPD) exposure, a single dose of 30 mg/kg/day 3-MCPD was administered to male Wistar rats for 40 days. Significant elevations of serum creatinine and blood urea nitrogen concentrations were observed on day 40, and urine N-acetyl-beta-D-glucosaminidase and beta-galactosidase (beta-Gal) activities were observed on day 20. Slight renal tubule hydropic degeneration and spermatozoa decreases were observed on day 10. The endogenous metabolite profile of rat urine was investigated by ultra performance liquid chromatography/mass spectrometry with electrospray ionization (ESI). Principal component analysis and partial least-squares enabled clusters to be visualized, with a trend of clustering on day 10 in ESI- and the greatest differences on days 30 and 40. Galactosylglycerol, a marker contributing to the clusters, which had earlier variations than conventional biomarkers and the most significant elevations as compared to other novel biomarkers, was first considered to be an early, sensitive biomarker in evaluating the effect of 3-MCPD exposure. The identification of galactosylglycerol was carried out by beta-Gal catalysis, and the possible mechanism of urine galactosylglycerol variation was elucidated.
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Cromatografía Líquida de Alta Presión/métodos , Glicerol/análogos & derivados , Espectrometría de Masa por Ionización de Electrospray/métodos , Acetilglucosaminidasa/metabolismo , Acetilglucosaminidasa/orina , Animales , Biomarcadores/sangre , Biomarcadores/metabolismo , Biomarcadores/orina , Nitrógeno de la Urea Sanguínea , Creatina/sangre , Galactósidos/orina , Glicerol/sangre , Glicerol/metabolismo , Glicerol/orina , Riñón/patología , Masculino , Análisis de Componente Principal , Ratas , Ratas Wistar , alfa-Clorhidrina , beta-Galactosidasa/metabolismo , beta-Galactosidasa/orinaRESUMEN
Recent chemopreventive studies from our group showed that dietary beta -ionone inhibited 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinogenesis by the inhibition of cell proliferation and apoptosis initiation. In this study, we examined the chemopreventive effects of varied doses of dietary beta -ionone on the development and growth of DMBA-induced rat mammary tumors as well as plasma antioxidant status. beta -ionone treatment groups were given 9, 18, and 36 mmol/kg in the AIN76A diet starting 2 wk prior to DMBA administration and continuing for the 24 wk. Results showed that tumor incidence was dose dependently reduced by 35.4, 68.3, and 87.8%, respectively, compared to the positive control. Tumor sizes were dose dependently smaller, and tumor weight was less in each group, each rat, and each tumor compared to the positive control (P < 0.05). A significant decrease in lipid peroxidation was observed in the tumor-induced rats treated with dietary beta -ionone, whereas the plasma activities of antioxidant enzymes such as glutathione peroxidase, glutathione reductase, superoxide dismutase, and the nonenzymatic antioxidant glutathione were increased in the beta -ionone treated rats when compared to control. The levels of catalase and lactate dehydrogenase were remarkably decreased in the beta -ionone treated groups compared to the positive control group. These results suggest that dietary beta -ionone has biologically relevant antioxidant activity and plays a chemopreventive role against DMBA induced mammary gland tumors.
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Anticarcinógenos/administración & dosificación , Antioxidantes/análisis , Dieta , Neoplasias Mamarias Experimentales/prevención & control , Norisoprenoides/administración & dosificación , 9,10-Dimetil-1,2-benzantraceno , Animales , Carcinógenos , Catalasa/sangre , Femenino , Glutatión/sangre , Glutatión Peroxidasa/sangre , Glutatión Reductasa/sangre , L-Lactato Deshidrogenasa/sangre , Peroxidación de Lípido , Neoplasias Mamarias Experimentales/sangre , Neoplasias Mamarias Experimentales/inducido químicamente , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Superóxido Dismutasa/sangreRESUMEN
OBJECTIVE: To investigate the attenuating effect of curcumin, an anti-inflammatory compound derived from dietary spice turmeric (Curcuma longa) on the pro-inflammatory insulin-resistant state in 3T3-L1 adipocytes. METHODS: Glucose uptake rate was determined with the [3H] 2-deoxyglucose uptake method. Expressions of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were measured by quantitative RT-PCR analysis and ELISA. Nuclear transcription factor kappaB p65 (NF-kappa p65) and mitogen-activated protein kinase (MAPKs) were detected by Western blot assay. RESULTS: The basal glucose uptake was not altered, and curcumin increased the insulin-stimulated glucose uptake in 3T3-L1 cells. Curcumin suppressed the transcription and secretion of TNF-alpha and IL-6 induced by palmitate in a concentration-dependent manner. Palmitate induced nuclear translocation of NF-kappaB. The activities of Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase1/2 (ERK1/2) and p38MAPK decreased in the presence of curcumin. Moreover, pretreatment with SP600125 (inhibitor of JNK) instead of PD98059 or SB203580 (inhibitor of ERK1/2 or p38MAPK, respectively) decreased the up-regulation of TNF-alpha induced by palmitate. CONCLUSION: Curcumin reverses palmitate-induced insulin resistance state in 3T3-L1 adipocytes through the NF-kappaB and JNK pathway.
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Antiinflamatorios no Esteroideos/farmacología , Curcumina/farmacología , Interleucina-6/metabolismo , Sistema de Señalización de MAP Quinasas , FN-kappa B/metabolismo , Palmitatos/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Células 3T3-L1 , Animales , Antracenos/farmacología , Glucosa/metabolismo , Insulina/farmacología , Resistencia a la Insulina , Interleucina-6/genética , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Ratones , Inhibidores de Proteínas Quinasas/farmacología , Factor de Necrosis Tumoral alfa/genética , Regulación hacia ArribaRESUMEN
beta-Ionone demonstrates potent anticancer activity both in vitro and in vivo. We determined tumor incidence and the number of rats bearing tumors as well as cell proliferation and apoptosis in a rat mammary cancer model induced by 7, 12-dimethylbenz[a]anthracene (DMBA). Rats were fed an AIN-76A diet containing beta-ionone (0, 9, 18 or 36 mmol/kg), starting 2 weeks before DMBA administration and continuing for 24 weeks. A dose-dependent inhibition of mammary carcinogenesis by dietary beta-ionone was observed. Corresponding tumor incidence values were 82.1, 53.3, 25.9 and 10.0% (p < 0.01 or 0.05). Time to tumor appearance increased and tumor multiplicity decreased with increasing dietary beta-ionone. Histopathological and immunohistochemical evaluations of tumors were performed on the 64, 31, 15 and 3 tumors, respectively, identified in rats from the respective groups of 30. The proportions of adenocarcinomas, adenomas and benign masses were equally distributed in the latter group. In proportions within the other groups, the proportions of adenocarcinomas and benign masses decreased and increased with increasing dietary beta-ionone. Proliferating cell nuclear antigen (PCNA), cyclin D1 and Bcl-2 expression decreased, and Bax expression and nuclear fragmentation increased with increasing dietary beta-ionone. These results demonstrate the potent capacity of dietary beta-ionone to suppress DMBA-initiated mammary cancer in rats.
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Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Neoplasias Mamarias Experimentales/prevención & control , Norisoprenoides/farmacología , 9,10-Dimetil-1,2-benzantraceno/toxicidad , Animales , Peso Corporal/efectos de los fármacos , Carcinógenos/toxicidad , Ciclina D1/metabolismo , Femenino , Neoplasias Mamarias Experimentales/inducido químicamente , Neoplasias Mamarias Experimentales/metabolismo , Neoplasias Mamarias Experimentales/patología , Antígeno Nuclear de Célula en Proliferación/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Conjugated linoleic acid (CLA) is a class of positional, geometric, conjugated dienoic isomers of linoleic acid. Dietary CLA supplementation has resulted in a dramatic decrease in body fat mass in mice. However, some but not all studies in mice and humans have found that CLA promoted insulin resistance, and there were conflicting reports on the effects of CLA on peroxisomal proliferator-activated receptor-gamma (PPAR gamma) activation and expression. The objective of present study was to investigate the effect of CLA on insulin resistance and its molecular mechanisms. Fifty male Wistar rats were randomly designed to the control, high-fat and high-fat with CLA (0.75, 1.50, and 3.00 g in per 100 g diet) groups. The effect of CLA on insulin sensitivity and the mechanism of resisting diabetes by CLA were investigated by RT-PCR assay. The results showed that supplementation with CLA significantly reduced body weight gain and white fat pad weight in the rats, the levels of plasma free fatty acids (FFA), triglycerides (TGs), cholesterin (TC), leptin, insulin and blood glucose concentration in the obese rats of CLA group were also decreased compared to the rats in the high-fat group. Dietary CLA increased the mRNA expression of PPAR gamma, fatty acid binding proteins (aP2), fatty acid transporter protein (FATP), acyl-CoA synthetase (ACS) and adiponectin in the adipose tissues of obese rats. The results suggest that CLA may ameliorate insulin resistance by activating PPAR gamma, and increasing the expression of PPAR gamma target genes such as ap2, FATP, FAT, and adiponectin in the white adipose tissue.
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Tejido Adiposo/metabolismo , Expresión Génica/efectos de los fármacos , Resistencia a la Insulina/genética , Ácidos Linoleicos Conjugados/administración & dosificación , PPAR gamma/genética , Adiponectina/genética , Adiponectina/metabolismo , Animales , Proteínas de Unión a Ácidos Grasos/genética , Proteínas de Unión a Ácidos Grasos/metabolismo , Ácidos Linoleicos Conjugados/farmacología , Masculino , Obesidad/genética , Obesidad/metabolismo , PPAR gamma/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas WistarRESUMEN
BACKGROUND: Human milk not only contains nutrients and antibodies, but also can be used as an indicator for levels of organic pollutants in human bodies. We developed a method for determining persistent organic pollutants (POPs) in the colostrum of women in preterm labor, the POPs of 36 colostrum samples have been examined. METHODS: Thirty-six samples of colostrum from preterm women were extracted by acetone-acetonitrile, enriched and purified by solid-phase Florisil columns. The purified POPs were further separated by the capillary columns, and detected by the gas chromatography-electron capture detection (GC-ECD). RESULTS: The average recovery rates of 6 types of organochlorine-based pesticides were 80.2%-112.1%, which represent the first 3 categories of the 12 species of POPs. The precise quantities detected were 3.85%-9.32% (the limits of detection were 0.03 microg/l to 0.08 microg/l), and the linear correlation coefficients were >or=0.9969. Of the 36 women tested, 10 (27.8%) were found to have colostrums containing traces of dichloro-diphenyl-trichloroethane (DDT), and 2 (5.56%) were tested positive for dieldrin. CONCLUSIONS: The combination of using GC-ECD proved to be both accurate and reliable, and this process proved to be both simple and time-effective. This method is applicable for determining the levels of POPs in organisms.
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Cromatografía de Gases/métodos , Calostro/química , Contaminantes Ambientales/análisis , Residuos de Plaguicidas/análisis , Adulto , Contaminantes Ambientales/aislamiento & purificación , Femenino , Humanos , Trabajo de Parto Prematuro , Residuos de Plaguicidas/aislamiento & purificación , EmbarazoRESUMEN
OBJECTIVE: To investigate the effects of maternal nutritional manipulation on fetal mRNA abundance of uncoupling protein UCP2, UCP3 and carnitine palmityl transferase 1 (CPT1), and find out an optimal maternal diet and targets for pharmacological prevention and treatment of obesity. METHODS: Wistar pregnant rats were assigned to two groups which received a standard diet (SD) and a high protein diet (HPD) during pregnancy, respectively. After delivery, the male offspring were assigned to control group (CON) and high protein group (HP) according to their maternal diet, which were suckled by dams that received SD during pregnancy. Offspring were fed with SD from weaning (week 3) to week 8. Then CON were allocated to two groups: CON (SD during the whole experiment); HFCON (high fat control). HFCON and HP group rats were fed with high-fat diet (HFD) for 6 wk to induce obesity. At 0, 3, 8 and 14 wk of age, blood and tissue were collected for analyzing blood fat and abundance of UCP2, 3 and CPT1 mRNA. RESULTS: In HP body weight and TG were decreased after weaning (F = 4.589, P = 0.039; F = 27.001, P = 0.000) and HFD (F = 16.076, P = 0.00; F = 71.518, P = 0.000). Obesity rates were significantly decreased in HP after HFD (chi2 = 8.076, P = 0.004). The abundance of UCP3 and CPT1 mRNA was persistently higher in HP than in CON or HFCON, and the abundance of UCP2 mRNA was also persistently higher than in CON or HFCON after weaning. Moreover the abundance of CPT1 mRNA was significantly increased after weaning and HFD compared with that after SD, the abundance of UCP2, UCP3 mRNA was also increased after HFD compared with that after SD. CONCLUSIONS: Increasing protein intake during pregnancy might prevent offspring from HFD-induced obesity in adult, moreover might increase offspring the expression of UCP2, UCP3 and CPT1 mRNA. UCP2, UCP3 and CPT1 might participate in prevention and treatment of obesity by mediating fatty acid oxidation.
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Carnitina O-Palmitoiltransferasa/metabolismo , Proteínas en la Dieta , Canales Iónicos/metabolismo , Proteínas Mitocondriales/metabolismo , Obesidad/metabolismo , Alimentación Animal , Animales , Animales Recién Nacidos , Femenino , Periodo Fértil , Masculino , Embarazo , ARN Mensajero/genética , Ratas , Ratas Wistar , Proteína Desacopladora 2 , Proteína Desacopladora 3Asunto(s)
Consumo de Bebidas Alcohólicas , Hígado Graso/prevención & control , Femenino , Humanos , MasculinoRESUMEN
The Songhua River is one of the biggest rivers in China and is the major freshwater source for industry and agriculture, as well as the source of the drinking water for millions of residents living along it. Heavy contamination of the Songhua River is due to domestic sewage and industrial wastewater. Thus, we set out to determine the carcinogenic potential of water samples taken from drinking water source of Harbin city in the Songhua River. Short-term genotoxic bioassays using Ames, SCE, and cell transformation assays were employed to examine the genotoxic activity of the ether extracts of water samples taken from the Songhua River. The results of the Ames test indicated that there were frame shift mutagens in the water samples, which were both direct and indirect. A dose-response relationship for the SCE assay was obtained, and the SCE cumulative frequency moved obviously to the right with increasing doses of water samples. Typical transformed foci were formed in NIH3T3 cells induced by ether extracts of water samples and the transformation frequency showed a dose-response relationship. The transformed cells showed the characteristics of malignant cells. All of the results indicated that the ether extracts of water samples taken from the Songhua River showed genotoxic activity.
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Compuestos Orgánicos/toxicidad , Contaminación Química del Agua , Animales , Transformación Celular Neoplásica , China , Humanos , Ratones , Pruebas de Mutagenicidad , Mutágenos/toxicidad , Células 3T3 NIH , Ríos , Salmonella typhimurium/genética , Intercambio de Cromátides HermanasRESUMEN
OBJECTIVE: To study the effects of conjugated linoleic acid (CLA) on expression of glucose transporter 4 (GLUT4) protein in skeletal muscle of insulin resistant rat, and explore the mechanism of resisting diabetes by CLA. METHODS: Male Wistar rats were randomly separated into control group, high-fat group and high fat plus CLA group (0.75 g%, 1.50 g%, 3.00 g% by deit weight), and the effects of CLA on blood glucose and insulin levels of insulin resistant rat were observed , by using Western blot technique to measure the expression level of GLUT4 protein in skeletal muscle of insulin resistant rat. RESULTS: The serum insulin and glucose levels of obese rats were (11.11 +/- 2.73) microU/ml, and (5.09 +/- 0.66) mmol/L, the supplement of CLA might decrease the hyperinsulinemia and hyperglycemia, and in CLA groups (0.75 g%, 1.50 g%, 3.00 g% by deit weight) the serum insulin was (6.99 +/- 1.77) microU/ml, (7.36 +/- 1.48) microU/ml and (7.85 +/- 1.60) microU/ml (P < 0.05), and the glucose levels were (4.28 +/- 0.72) mmol/L, (4.18 +/- 0.55) mmol/L (P < 0.05), (4.06 +/- 0.63) mmol/L (P < 0.05) respectively. The expression of GLUT4 protein in skeletal muscle of rat fed with high fat diet were decreased as compared with those fed with basic deit, and CLA might increase the expression of GLUT4 protein in skeletal muscle fed with high fat diet. CONCLUSIONS: CLA improve the insulin resistance of obese rat, possibly acting through increasing the expression of GLUT4 protein in skeletal muscle of rat fed with high fat diet.
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Transportador de Glucosa de Tipo 4/metabolismo , Resistencia a la Insulina , Ácido Linoleico/farmacología , Animales , Glucemia/metabolismo , Insulina/sangre , Masculino , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
Colorectal cancer (CRC) is among the most common and fatal forms of solid tumors worldwide and more than two thirds of CRC and adenomas patients have APC gene mutations. APC is a key regulator in the Wnt/ß-catenin signaling pathway but its roles in CRC remains to be elucidated. In this study, we compared APC genes between CRC patients and controls to determine possible associations of nucleotide changes in the APC gene with the pathways involved in CRC pathogenesis. All participants received physical and enteroscopic examinations. The APC gene was sequenced for 300 Chinese Han CRC patients and 411 normal controls, and the expression levels of genes in the signaling pathway were analyzed using Western Blotting. Statistical analyses were conducted using SPSS (version 19.0) software. We found that rs11954856 in the APC gene was associated with colorectal cancer and could increase the expression levels of APC, ß-catenin, TCF7L1, TCF7L2 and LEF1 genes in the pathway in the CRC patients, demonstrating the involvement of APC in the pathological processes leading to CRC.