RESUMO
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver diseases. Cyclocarya paliurus (C. paliurus), an edible and medicinal plant in Chinese folk, has been demonstrated to ameliorate diabetes, obesity and lipid metabolism disorders. However, its effects on NAFLD and its potential molecular mechanism have not been clearly expounded. PURPOSE: The present study was designed to explore the therapeutic potential of triterpenic acids-enriched fraction from C. paliurus (CPT), as well as its underlying mechanism in vivo and in vitro models of NAFLD. METHODS: The metabolic effects and possible molecular mechanism of CPT were examined using HepG2 cells and primary hepatocytes (isolated from C57BL/6â¯J mice) models of fatty liver induced by palmitic acid (PA) and a high fat diet mouse model. RESULTS: In high fat diet-induced C57BL/6â¯J mice, CPT significantly reduced liver weight index, serum alanine transaminase (ALT), aspartate transaminase (AST), triacylglycerol (TG), total cholesterol (TC) and hepatic TG, TC levels. Moreover, CPT dramatically decreased the contents of blood glucose, insulin, and insulin resistance (HOMA-IR) index. Meanwhile, CPT significantly increased the tyrosine phosphorylation level of IRS and the uptake of 2-deoxyglucose (2DG) in PA-induced HepG2 cells and primary hepatocytes fatty liver models. Furthermore, in PA-induced HepG2 cells and primary hepatocytes, CPT significantly decreased the number of lipid droplets and intracellular TG content. In addition, mechanism investigation showed that CPT increased the phosphorylation of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt) and glycogen synthase-3ß (GSK3ß) in vivo and in vitro models, which were abrogated by PI3K inhibitor LY294002 in vitro models. CONCLUSION: These findings indicate that CPT may exert the therapeutic effects on NAFLD via regulating PI3K/Akt/GSK3ß pathway.
Assuntos
Juglandaceae/química , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Extratos Vegetais/farmacologia , Triterpenos/farmacologia , Animais , Glicemia/metabolismo , Dieta Hiperlipídica/efeitos adversos , Glicogênio Sintase Quinase 3 beta/metabolismo , Células Hep G2 , Hepatócitos/metabolismo , Humanos , Insulina/metabolismo , Resistência à Insulina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinase/metabolismo , Fosforilação , Extratos Vegetais/química , Plantas Medicinais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Triglicerídeos/metabolismo , Triterpenos/químicaRESUMO
AIMS/INTRODUCTION: To explore the relationship between plasma iron levels and gestational diabetes mellitus, as well as its impact on macrosomia. MATERIALS AND METHODS: We retrospectively compared ferritin level and other characteristics between pregnant women with gestational diabetes mellitus (GDM) and pregnant women without GDM. The correlation between the levels of plasma ferritin, glucose and hemoglobin was explored. Meanwhile, we assessed the risk factors of macrosomia. Furthermore, we explored the relationship between ferritin level and the incidence of macrosomia. RESULTS: A total of 793 pregnant women were enrolled in the present study, of which 92 pregnant women had GDM and 701 pregnant women were healthy. Meanwhile, 51 pregnant women gave birth to infants with macrosomia and another 742 women had normal infants. Compared with non-GDM women, pregnant women with GDM were older, with higher pre-pregnancy body mass index, plasma ferritin, fasting plasma glucose, 1-h postprandial glucose, 2-h plasma glucose and hemoglobin. In addition, our results showed a significant positive correlation between the levels of ferritin and fasting plasma glucose when ferritin levels were >70 ng/mL. Our results also showed that pre-pregnancy overweight or obesity, a high concentration of ferritin, as well as abnormal levels of fasting plasma glucose, 1-h plasma glucose and 2 h plasma glucose were risk factors for macrosomia. Furthermore, as the level of ferritin increased, so did the incidence of macrosomia. CONCLUSIONS: The current study provides evidence that pregnant women with high levels of ferritin might be prone to GDM. In addition, a high level of ferritin might be an independent risk factor for macrosomia. Therefore, the negative effect of iron supplementation in non-anemic pregnant women might be noteworthy.