Navegando por Autor "Zangerolamo, Lucas"
Agora exibindo 1 - 2 de 2
Resultados por página
Opções de Ordenação
Item Energy homeostasis deregulation is attenuated by TUDCA treatment in streptozotocin‐induced Alzheimer’s disease mice model.(2021) Zangerolamo, Lucas; Solon, Carina; Soares, Gabriela Moreira; Engel, Daiane Fátima; Velloso, Licio Augusto; Boschero, Antonio Carlos; Carneiro, Everardo Magalhães; Sampaio, Helena Cristina L. BarbosaAlzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. While cognitive defcits remain the major manifestation of AD, metabolic and non- cognitive abnormalities, such as alterations in food intake, body weight and energy balance are also present, both in AD patients and animal models. In this sense, the tauroursodeoxycholic acid (TUDCA) has shown benefcial efects both in reducing the central and cognitive markers of AD, as well as in attenuating the metabolic disorders associated with it. We previously demonstrated that TUDCA improves glucose homeostasis and decreases the main AD neuromarkers in the streptozotocin- induced AD mouse model (Stz). Besides that, TUDCA-treated Stz mice showed lower body weight and adiposity. Here, we investigated the actions of TUDCA involved in the regulation of body weight and adiposity in Stz mice, since the efects of TUDCA in hypothalamic appetite control and energy homeostasis have not yet been explored in an AD mice model. The TUDCA-treated mice (Stz+TUDCA) displayed lower food intake, higher energy expenditure (EE) and respiratory quotient. In addition, we observed in the hypothalamus of the Stz+TUDCA mice reduced fuorescence and gene expression of infammatory markers, as well as normalization of the orexigenic neuropeptides AgRP and NPY expression. Moreover, leptin-induced p-JAK2 and p-STAT3 signaling in the hypothalamus of Stz +TUDCA mice was improved, accompanied by reduced acute food intake after leptin stimulation. Taken together, we demonstrate that TUDCA treatment restores energy metabolism in Stz mice, a phenomenon that is associated with reduced food intake, increased EE and improved hypothalamic leptin signaling. These fndings suggest treatment with TUDCA as a promising therapeutic intervention for the control of energy homeostasis in AD individuals.Item The bile acid TUDCA improves glucose metabolism in streptozotocin-induced Alzheimer’s disease mice model.(2021) Zangerolamo, Lucas; Vettorazzi, Jean Franciesco; Solon, Carina; Bronczek, Gabriela Alves; Engel, Daiane Fátima; Kurauti, Mirian Ayumi; Soares, Gabriela Moreira; Rodrigues, Karina S.; Velloso, Licio Augusto; Boschero, Antonio Carlos; Carneiro, Everardo Magalhães; Barbosa, Helena Cristina de LimaAlzheimer’s disease (AD) is a neurodegenerative disorder and the major cause of dementia. According to pre- dictions of the World Health Organization, more than 150 million people worldwide will suffer from dementia by 2050. An increasing number of studies have associated AD with type 2 diabetes mellitus (T2DM), since most of the features found in T2DM are also observed in AD, such as insulin resistance and glucose intolerance. In this sense, some bile acids have emerged as new therapeutic targets to treat AD and metabolic disorders. The taurine conjugated bile acid, tauroursodeoxycholic (TUDCA), reduces amyloid oligomer accumulation and improves cognition in APP/PS1 mice model of AD, and also improves glucose-insulin homeostasis in obese and type 2 diabetic mice. Herein, we investigated the effect of TUDCA upon glucose metabolism in streptozotocin-induced AD mice model (Stz). The Stz mice that received 300 mg/kg TUDCA during 10 days (Stz + TUDCA), showed improvement in glucose tolerance and insulin sensitivity, reduced fasted and fed glycemia, increased islet mass and β-cell area, as well as increased glucose-stimulated insulin secretion, compared with Stz mice that received only PBS. Stz + TUDCA mice also displayed lower neuroinflammation, reduced protein content of amyloid oligomer in the hippocampus, improved memory test and increased protein content of insulin receptor β-subunit in the hippocampus. In conclusion, TUDCA treatment enhanced glucose homeostasis in the streptozotocin- induced Alzheimer’s disease mice model, pointing this bile acid as a good strategy to counteract glucose ho- meostasis disturbance in AD pathology.