RESUMO
CONTEXT: The role of silymarin in hepatic lipid dysfunction and its possible mechanisms of action were investigated. OBJECTIVE: To evaluate the effects of silymarin on hepatic and metabolic profiles in mice fed with 30% fructose for 8 weeks. METHODS: We evaluated the antioxidant profile of silymarin; mice consumed 30% fructose and were treated with silymarin (120 mg/kg/day or 240 mg/kg/day). We performed biochemical, redox status, and histopathological assays. RT-qPCR was performed to detect ACC-1, ACC-2, FAS, and CS expression, and western blotting to detect PGC-1α levels. RESULTS: Silymarin contains high levels of phenolic compounds and flavonoids and exhibited significant antioxidant capacity in vitro. In vivo, the fructose-fed groups showed increased levels of AST, ALT, SOD/CAT, TBARS, hepatic TG, and cholesterol, as well as hypertriglyceridaemia, hypercholesterolaemia, and increased ACC-1 and FAS. Silymarin treatment reduced these parameters and increased mRNA levels and activity of hepatic citrate synthase. CONCLUSIONS: These results suggest that silymarin reduces worsening of NAFLD.
RESUMO
The aim of the present study was to investigate the participation of the sympathetic nervous system (SNS) in the control of glycerol-3-P (G3P) generating pathways in white adipose tissue (WAT) of rats in three situations in which the plasma insulin levels are low. WAT from 48 h fasted animals, 3 day-streptozotocin diabetic animals and high-protein, carbohydrate-free (HP) diet-fed rats was surgical denervated and the G3P generation pathways were evaluated. Food deprivation, diabetes and the HP diet provoke a marked decrease in the rate of glucose uptake and glycerokinase (GyK) activity, but a significant increase in the glyceroneogenesis, estimated by the phosphoenolpyruvate carboxykinase (PEPCK) activity and the incorporation of 1-[(14)C]-pyruvate into glycerol-TAG. The denervation provokes a reduction (~70%) in the NE content of WAT in fasted, diabetic and HP diet-fed rats. The denervation induced an increase in WAT glucose uptake of fed, fasted, diabetic and HP diet-fed rats (40%, 60%, 3.2 fold and 35%, respectively). TAG-glycerol synthesis from pyruvate was reduced by denervation in adipocytes of fed (58%) and fasted (36%), saline-treated (58%) and diabetic (23%), and HP diet-fed rats (11%). In these same groups the denervation reduced the PEPCK mRNA expression (75%-95%) and the PEPCK activity (35%-60%). The denervation caused a ~35% decrease in GyK activity of control rats and a further ~35% reduction in the already low enzyme activity of fasted, diabetic and HP diet-fed rats. These data suggest that the SNS plays an important role in modulating G3P generating pathways in WAT, in situations where insulin levels are low.