RESUMEN
Dehydroepiandrosterone (DHEA) possesses fat-reducing effect, while little information is available on whether DHEA regulates cell proliferation and mitochondrial function, which would, in turn, affect lipid droplet accumulation in the broiler. In the present study, the lipid droplet accumulation, cell proliferation, cell cycle and mitochondrial membrane potential were analysis in primary chicken hepatocytes after DHEA treated. The results showed that total area and counts of lipid droplets were significantly decreased in hepatocytes treated with DHEA. The cell viability was significantly increased, while cell proliferation was significantly inhibited in a dose dependent manner in primary chicken hepatocytes after DHEA treated. DHEA treatment significantly increased the cell population in S phase and decreased the population in G2/M in primary chicken hepatocytes. Meanwhile, the cyclin A and cyclin-dependent kinases 2 (CDK2) mRNA abundance were significantly decreased in hepatocytes after DHEA treated. No significant differences were observed in the number of mitochondria, while the mitochondrial membrane permeability and succinate dehydrogenase (SDH) activity were significantly increased in hepatocytes after DHEA treated. In conclusion, our results demonstrated that DHEA reduced lipid droplet accumulation by inhibiting hepatocytes proliferation and enhancing mitochondrial function in primary chicken hepatocytes.
Asunto(s)
Proliferación Celular/efectos de los fármacos , Deshidroepiandrosterona/farmacología , Hepatocitos/efectos de los fármacos , Gotas Lipídicas/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Animales , Ciclo Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Embrión de Pollo , Evaluación Preclínica de Medicamentos , Metabolismo de los Lípidos/efectos de los fármacos , Cultivo Primario de CélulasRESUMEN
(-)-Hydroxycitric acid (HCA), a major component of Garcinia cambogia extracts, has been shown to suppress BW gain and fat accumulation in animals and humans. However, the mechanism remains unknown. In this study, gas chromatography-mass spectrometry was used to analyse serum metabolites, and principal component analysis and partial least-squares-discriminant analysis models were generated to analyse serum metabolite changes in broiler chickens after the administration of (-)-HCA at 0, 1000, 2000 and 3000 mg/kg diets for 28 days. Metabolites showing significant changes were screened by 'variable importance in the projection' plots. The results showed that 20 metabolites in the 1000 mg/kg (-)-HCA treatment group and 16 metabolites in 3000 mg/kg (-)-HCA treatment group were significantly altered. Metabolites pathway enrichment analysis indicated that these metabolites were mainly associated with metabolism of amino acids, protein synthesis, citric acid cycle, and uric acid and fatty acid synthesis. The data indicated that (-)-HCA promoted protein synthesis by regulating the metabolic directions of amino acids. At the same time, (-)-HCA treatment inhibited fatty acid synthesis by promoting the citric acid cycle, resulting in reduced cytosolic acetyl-CoA content in broiler chickens. The present study identified global changes in metabolites and analysed the main canonical metabolic pathways in broiler chickens supplemented with (-)-HCA. These results will deepen our understanding of the mechanism of (-)-HCA's effects in animals.
Asunto(s)
Pollos/metabolismo , Citratos/farmacología , Suplementos Dietéticos , Ácidos Grasos/biosíntesis , Metabolómica , Adipogénesis , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Citratos/química , Dieta/veterinaria , Relación Dosis-Respuesta a Droga , Garcinia cambogia/química , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Extractos Vegetales/farmacología , Biosíntesis de ProteínasRESUMEN
The aim of the current study was to evaluate the effect of chronic dehydroepiandrosterone (DHEA) administration on steroid hormones and antioxidant parameters in aged rats. To this end, three groups of Sprague-Dawley rats were compared: young (3 months of age) untreated; aged (19 months old) untreated; and aged rats treated with 20 mg/kg DHEA for 8 weeks. Major organs of aged rats in the untreated group demonstrated physiological atrophy, compared to those of young rats; this effect appeared to have been partially reversed by DHEA treatment. Testosterone and estradiol contents were significantly decreased and aldosterone significantly increased in aged untreated, compared to young untreated rats. Steroid hormone levels were obviously reversed, however, in aged rats treated with DHEA. Additionally, superoxide dismutase activity in serum, brain, heart, and liver was decreased, and maleic dialdehyde content in heart was markedly increased in untreated aged, compared to young, rats. Importantly, these changes in brain and heart of aged rats were reversed by DHEA treatment. Heme oxygenase mRNA levels were increased and inducible nitric oxide synthase mRNA levels decreased in aged, compared to young, rats; DHEA treatment appeared to reverse these changes. These results indicate that chronic DHEA administration may have effects on steroid hormone levels and antioxidant parameters in aged rats and result in postponement of the aging process.
Asunto(s)
Envejecimiento/sangre , Deshidroepiandrosterona/farmacología , Aldosterona/sangre , Animales , Antioxidantes/metabolismo , Peso Corporal/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Estradiol/sangre , Expresión Génica/efectos de los fármacos , Glutarredoxinas/genética , Glutarredoxinas/metabolismo , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Masculino , Malondialdehído/sangre , Miocardio/enzimología , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Especificidad de Órganos , Oxidación-Reducción , Ratas Sprague-Dawley , Superóxido Dismutasa/sangre , Testosterona/sangreRESUMEN
The TRPC3 channel, an intensively studied member of the widely expressed transient receptor potential (TRP) family, is a Ca(2+)-conducting channel activated in response to phospholipase C-coupled receptors. Despite scrutiny, the receptor-induced mechanism to activate TRPC3 channels remains unclear. Evidence indicates TRPC3 channels interact directly with intracellular inositol 1,4,5-trisphosphate receptors (InsP(3)Rs) and that channel activation is mediated through coupling to InsP(3)Rs. TRPC3 channels were expressed in DT40 chicken B lymphocytes in which all three InsP(3)R genes were deleted (DT40InsP(3)R-k/o). Endogenous B-cell receptors (BCR) coupled through Syk kinase to phospholipase C-gamma (PLC-gamma) activated the expressed TRPC3 channels in both DT40w/t and DT40InsP(3)R-k/o cells. The diacylglycerol (DAG) analogue 1-oleoyl-2-acetyl-sn-glycerol (OAG) also activated TRPC3 channels independently of InsP(3)Rs. BCR-induced TRPC3 activation was blocked by the PLC enzymic inhibitor, U-73122, and also blocked by wortmannin-induced PLC substrate depletion. Neither U-73122 nor wortmannin modified either OAG-induced TRPC3 activation or store-operated channel activation in DT40 cells. Cotransfection of cells with both G protein-coupled M5 muscarinic receptors and TRPC3 channels resulted in successful M5 coupling to open TRPC3 channels mediated by PLC-beta. We conclude that TRPC3 channels are activated independently of InsP(3)Rs through DAG production resulting from receptor-mediated activation of either PLC-gamma or PLC-beta.
Asunto(s)
Canales de Calcio/genética , Canales Iónicos/biosíntesis , Receptores Citoplasmáticos y Nucleares/genética , Androstadienos/farmacología , Animales , Animales Modificados Genéticamente , Linfocitos B/metabolismo , Calcio/metabolismo , Canales de Calcio/fisiología , Línea Celular , Células Cultivadas , Pollos , ADN Complementario/metabolismo , Inhibidores Enzimáticos/farmacología , Precursores Enzimáticos/metabolismo , Estrenos/farmacología , Receptores de Inositol 1,4,5-Trifosfato , Péptidos y Proteínas de Señalización Intracelular , Isoenzimas/metabolismo , Ratones , Mutación , Fosfolipasa C gamma , Plásmidos/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Pirrolidinonas/farmacología , Receptores de Antígenos de Linfocitos B/metabolismo , Receptores Citoplasmáticos y Nucleares/fisiología , Quinasa Syk , Canales Catiónicos TRPC , Factores de Tiempo , Transfección , Fosfolipasas de Tipo C/metabolismo , WortmaninaRESUMEN
OBJECTIVE: To study the prevalence and pathogenesis of hypopituitarism following tuberculous meningitis in childhood. DESIGN: A retrospective cross-sectional study. SETTING: A university teaching hospital and a tuberculosis referral center. PATIENTS: Forty-nine patients, aged 23.4 +/- 6.0 years (mean +/- SD), who had tuberculous meningitis in childhood (age at diagnosis, 5.9 +/- 5.0 years) were studied. MEASUREMENTS: A detailed assessment of hypothalamic-pituitary function, including conventional stimulation tests and responses to four hypothalamic releasing hormones, was done. Magnetic resonance imaging of the hypothalamic-pituitary region was performed in patients with abnormal endocrine function. RESULTS: Ten patients were found to have abnormal pituitary function: Seven had growth hormone deficiency, four of whom also had gonadotropin deficiency; the other three had gonadotropin deficiency, corticotropin deficiency, and mild hyperprolactinemia, respectively; none had diabetes insipidus. Among those with growth hormone deficiency, a significant correlation (r = 0.749, P < 0.05) was found between the height standard deviation score and the age at diagnosis of tuberculous meningitis. Growth hormone, corticotropin, and gonadotropin responses to growth hormone releasing hormone, corticotropin releasing hormone, and gonadotropin releasing hormone, respectively, suggested a hypothalamic defect in five patients. Magnetic resonance imaging scans of the hypothalamic-pituitary region were abnormal in five patients. CONCLUSIONS: Hypopituitarism was documented in 20% of a small subset of patients years after recovery from tuberculous meningitis in childhood. The cause appears to be tuberculous lesions affecting the hypothalamus, pituitary stalk and, directly or indirectly, the pituitary itself. Early recognition and treatment can be beneficial.