RESUMO
Obesity is closely linked with metabolic diseases, while life and prenatal exposure to endocrine-disrupting chemicals has been implicated in the development of obesity. Magnesium lithospermate B (MLB), an active compound of Salvia miltiorrhiza (Danshen), has beneficial effects on insulin resistance and metabolic abnormalities in diet-induced obese rodents. Since exposure to endocrine-disrupting chemical Bisphenol A (BPA) during pregnancy mimics the effects of high fat diet-induced alterations of glucose and lipid metabolism in adult male offspring, the effects of daily MLB supplementation for 4 weeks on metabolic abnormalities in rats weaning from prenatal BPA-exposed dams were investigated. BPA-exposed rats developed obesity and adiposity concurrent with hyperglycemia, hyperinsulinemia, insulin resistance, hypertriglyceridemia, and elevation of circulating glucagon and free fatty acids. Increased hepatic fatty acid synthesis and decreased fatty acid ß-oxidation, activation of adipocytic adipogenesis, maturation, and lipogenesis, as well as reduction of muscular glucose uptake were demonstrated in BPA-exposed rats. The aforementioned alterations were improved by MLB supplementation. Additionally, MLB displayed negative effects on glucocorticoid receptor action and inflammation, and promoted lipolysis and thermogenesis in the adipose tissues. In conclusion, our findings suggest that MLB may be a potential therapeutic compound against metabolic diseases, including maternal exposure-induced metabolic abnormalities.
Assuntos
Compostos Benzidrílicos , Efeitos Tardios da Exposição Pré-Natal , Animais , Compostos Benzidrílicos/toxicidade , Suplementos Nutricionais , Medicamentos de Ervas Chinesas , Feminino , Masculino , Fenóis/toxicidade , Gravidez , RatosRESUMO
Atypical antipsychotics, such as olanzapine, are commonly prescribed to patients with schizophrenic symptoms and other psychiatric disorders. However, weight gain and metabolic disturbance cause adverse effects, impair patient compliance and limit clinical utility. Thus, a better understanding of treatment-acquired adverse effects and identification of targets for therapeutic intervention are believed to offer more clinical benefits for patients with schizophrenia. Beyond its nutritional effects, studies have indicated that supplementation of chromium brings about beneficial outcomes against numerous metabolic disorders. In this study, we investigated whether olanzapine-induced weight gain and metabolic disturbance involved chromium dynamic mobilization in a female Sprague-Dawley rat model, and whether a dietary supplement of chromium improved olanzapine-acquired adverse effects. Olanzapine medicated rats experienced weight gain and adiposity, as well as the development of hyperglycemia, hyperinsulinemia, insulin resistance, hyperlipidemia, and inflammation. The olanzapine-induced metabolic disturbance was accompanied by a decrease in hepatic Akt and AMP-activated Protein Kinase (AMPK) actions, as well as an increase in serum interleukin-6 (IL-6), along with tissue chromium depletion. A daily intake of chromium supplements increased tissue chromium levels and thermogenic uncoupling protein-1 (UCP-1) expression in white adipose tissues, as well as improved both post-olanzapine weight gain and metabolic disturbance. Our findings suggest that olanzapine medicated rats showed a disturbance of tissue chromium homeostasis by inducing tissue depletion and urinary excretion. This loss may be an alternative mechanism responsible for olanzapine-induced weight gain and metabolic disturbance.