RESUMEN
Black bean (Phaseolus vulgaris L.) seed coats are a rich source of natural compounds with potential beneficial effects on human health. Beans exert hypolipidaemic activity; however, this effect has not been attributed to any particular component, and the underlying mechanisms of action and protein targets remain unknown. The aim of the present study was to identify and quantify primary saponins and flavonoids extracted from black bean seed coats, and to study their effects on lipid metabolism in primary rat hepatocytes and C57BL/6 mice. The methanol extract of black bean seed coats, characterised by a HPLC system with a UV-visible detector and an evaporative light-scattering detector and HPLC-time-of-flight/MS, contained quercetin 3-O-glucoside and soyasaponin Af as the primary flavonoid and saponin, respectively. The extract significantly reduced the expression of SREBP1c, FAS and HMGCR, and stimulated the expression of the reverse cholesterol transporters ABCG5/ABCG8 and CYP7A1 in the liver. In addition, there was an increase in the expression of hepatic PPAR-α. Consequently, there was a decrease in hepatic lipid depots and a significant increase in bile acid secretion. Furthermore, the ingestion of this extract modulated the proportion of lipids that was used as a substrate for energy generation. Thus, the results suggest that the extract of black bean seed coats may decrease hepatic lipogenesis and stimulate cholesterol excretion, in part, via bile acid synthesis.
Asunto(s)
Colagogos y Coleréticos/uso terapéutico , Suplementos Dietéticos , Flavonoides/uso terapéutico , Lipotrópicos/uso terapéutico , Phaseolus/química , Saponinas/uso terapéutico , Semillas/química , Animales , Ácidos y Sales Biliares/metabolismo , Células Cultivadas , Colagogos y Coleréticos/química , Colagogos y Coleréticos/aislamiento & purificación , Colagogos y Coleréticos/metabolismo , Colesterol/metabolismo , Flavonoides/química , Flavonoides/aislamiento & purificación , Flavonoides/metabolismo , Regulación de la Expresión Génica , Hepatocitos/citología , Hepatocitos/enzimología , Hepatocitos/metabolismo , Metabolismo de los Lípidos , Lipotrópicos/química , Lipotrópicos/aislamiento & purificación , Lipotrópicos/metabolismo , Receptores X del Hígado , Masculino , México , Ratones , Ratones Endogámicos C57BL , Receptores Nucleares Huérfanos/agonistas , Receptores Nucleares Huérfanos/genética , Receptores Nucleares Huérfanos/metabolismo , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/metabolismo , Extractos Vegetales/uso terapéutico , Distribución Aleatoria , Ratas , Saponinas/química , Saponinas/aislamiento & purificación , Saponinas/metabolismoRESUMEN
The literature has associated hepatic insulin action with NAFLD. In this sense, treatments to revert steatosis and improve hepatic insulin action become important. Our group has demonstrated that inhibition of Sterol Regulatory Element Binding Proteins-1c (SREBP-1c) reverses hepatic steatosis. However, insulin signals after NAFLD reversion require better investigation. Thus, in this study, we investigated if the reversal of NAFLD by SREBP-1c inhibitor results in improvement in the hepatic insulin signal in obesity mice. After installation/achievement of diet-induced obesity and insulin resistance, Swiss mice were divided into 3 groups: i) Lean, ii) D-IHS, diet-induced hepatic steatosis [no treatment with antisense oligonucleotide (ASO)], and iii) RD-IHS, reversion of diet-induced hepatic steatosis (treated with ASO). The mice were treated with ASO SREBP-1c as previously described by our group. After ASO treatment, one set of animals was anesthetized and used for in vivo test, and another mice set was anesthetized and used for histology and Western blot analysis. Reversion of diet-induced hepatic steatosis did not change blood glucose, glucose decay constant (k(ITT)), body weight, or serum insulin levels. In addition, results showed that the protocol did not improve insulin pathway signaling, as confirmed by the absence of changes in IR, IRS1, Akt and Foxo1 phosphorylation in hepatic tissue. In parallel, no alterations were observed in proinflammatory molecules. Thus, our results suggest that the inhibition of SREBP-1c reverts steatosis, but without improving insulin hepatic resistance.
Asunto(s)
Hígado Graso/prevención & control , Resistencia a la Insulina , Lipotrópicos/uso terapéutico , Hígado/efectos de los fármacos , Obesidad/fisiopatología , Oligonucleótidos Antisentido/uso terapéutico , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/antagonistas & inhibidores , Animales , Dieta Alta en Grasa/efectos adversos , Hígado Graso/etiología , Hígado Graso/inmunología , Inyecciones Intraperitoneales , Insulina/sangre , Insulina/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Lipotrópicos/administración & dosificación , Hígado/inmunología , Hígado/metabolismo , Hígado/patología , Masculino , Ratones , Enfermedad del Hígado Graso no Alcohólico , Obesidad/etiología , Obesidad/metabolismo , Obesidad/patología , Oligonucleótidos Antisentido/administración & dosificación , Fosforilación/efectos de los fármacos , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Distribución Aleatoria , Receptor de Insulina/metabolismo , Transducción de Señal/efectos de los fármacos , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismoRESUMEN
OBJECTIVE: To evaluate prenatal treatment with hydroxycobalamin (OH-Cbl) in a pregnancy at risk for a severe form of the cobalamin C defect and postnatal treatment of the affected child. STUDY DESIGN: Observational study with non-randomized intervention. RESULTS: In contrast to reported pregnancies with affected fetuses in which maternal methylmalonic aciduria was found in the last trimester of pregnancy, there was no maternal methylmalonic aciduria in our case, given prenatal treatment with intramuscular OH-Cbl. We did not find that the concentration of odd long-chain fatty acids in cord blood erythrocytes reflects fetal methylmalonic academia. After birth, the infant was treated with intramuscular OH-Cbl and oral carnitine. Oral folate and betaine were added as adjunct therapy to decrease plasma total homocysteine. Because of inadequate metabolic control, a diet reduced in natural protein was introduced. The child had normal developmental milestones but had nystagmus, hyperpigmented retinopathy, and discrete truncal muscular hypotonia. CONCLUSIONS: Despite prenatal and postnatal treatment, adequate metabolic control, absence of metabolic crises, and normal developmental milestones, this patient with the cobalamin C defect had characteristic symptoms of the disease.
Asunto(s)
Hematínicos/uso terapéutico , Hidroxocobalamina/uso terapéutico , Errores Innatos del Metabolismo/tratamiento farmacológico , Deficiencia de Vitamina B 12/tratamiento farmacológico , Deficiencia de Vitamina B 12/genética , Betaína/uso terapéutico , Carnitina/uso terapéutico , Femenino , Ácido Fólico/uso terapéutico , Hematínicos/administración & dosificación , Humanos , Hidroxocobalamina/administración & dosificación , Recién Nacido , Lipotrópicos/uso terapéutico , Masculino , Errores Innatos del Metabolismo/diagnóstico , Embarazo , Atención Prenatal , Diagnóstico Prenatal , Deficiencia de Vitamina B 12/diagnósticoRESUMEN
Non-alcoholic steatohepatitis (NASH) is a chronic liver disease that occurs in patients with no significant alcohol consumption; it is not histologically different from alcoholic hepatitis because it presents macrovesicular steatosis, hepatocellular necrosis, mixed inflammatory infiltrate, and various stages of fibrosis in addition Mallory bodies in some patients. Some authors have even described NASH as a benign disease; however, it is presently considered a potentially serious disease that may evolve into liver cirrhosis and probably, liver cancer. It is more often related to female sex, obesity, and dyslipidemia, although it may be present in other population groups and associated with other factors. Its origin may be multifactorial, including insulin resistance, protein glycation, oxidative stress, and others. The disease may be asymptomatic and found in routine physical exams when the patient shows increased aminotransferases with no other explanation. At present the only specific diagnosis procedure is liver biopsy. The sole available current treatment is body weight control, normalizing glucose and lipid blood levels, as well as the administration of some medication, as illustrated in the subsequent article.
Asunto(s)
Hígado Graso , Hepatitis , Acetilcisteína/administración & dosificación , Acetilcisteína/uso terapéutico , Adolescente , Adulto , Factores de Edad , Antioxidantes/administración & dosificación , Antioxidantes/uso terapéutico , Betaína/administración & dosificación , Betaína/uso terapéutico , Niño , Colagogos y Coleréticos/administración & dosificación , Colagogos y Coleréticos/uso terapéutico , Ensayos Clínicos como Asunto , Complicaciones de la Diabetes , Hígado Graso/epidemiología , Hígado Graso/etiología , Hígado Graso/patología , Hígado Graso/terapia , Femenino , Depuradores de Radicales Libres/administración & dosificación , Depuradores de Radicales Libres/uso terapéutico , Hepatitis/epidemiología , Hepatitis/etiología , Hepatitis/patología , Hepatitis/terapia , Humanos , Hiperlipidemias/complicaciones , Resistencia a la Insulina , Lipotrópicos/administración & dosificación , Lipotrópicos/uso terapéutico , Hígado/patología , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/terapia , Proyectos Piloto , Pronóstico , Factores de Riesgo , Factores Sexuales , Factores de Tiempo , Ácido Ursodesoxicólico/administración & dosificación , Ácido Ursodesoxicólico/uso terapéutico , Vitamina E/administración & dosificación , Vitamina E/uso terapéutico , Pérdida de PesoRESUMEN
Se basa en los resultados de un ensayo clínico del medicamento PPG en pacientes con disfunciones sexuales, los autores exponen que los pacientes que eran aceptados en el estudio se les realizaba numerosos exámenes complementarios y exponen las ventajas obtenidas