Energy homeostasis deregulation is attenuated by TUDCA treatment in streptozotocin-induced Alzheimer's disease mice model

Autor(es)

Zangerolamo, Lucas ^[1] ; Solon, Carina ^[2] ; Soares, Gabriela M. ^[1] ; Engel, Daiane F. ^[2] ; Velloso, Licio A. ^[2] ; Boschero, Antonio C. ^[1] ; Carneiro, Everardo M. ^[1] ; Barbosa, Helena Cristina L. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, UNICAMP, Obes & Comorbid Res Ctr, Dept Struct & Funct Biol, Campinas, SP - Brazil

^[2] Univ Estadual Campinas, UNICAMP, Obes & Comorbid Res Ctr, Lab Cell Signaling, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 11, n. 1 SEP 13 2021.
• Citações Web of Science: 0

Resumo

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. While cognitive deficits 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 beneficial effects 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 effects 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 fluorescence and gene expression of inflammatory 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 findings suggest treatment with TUDCA as a promising therapeutic intervention for the control of energy homeostasis in AD individuals. (AU)

• Processo FAPESP: 13/07607-8 - CMPO - Centro Multidisciplinar de Pesquisa em Obesidade e Doenças Associadas
• Beneficiário: Licio Augusto Velloso
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 18/20213-2 - Papel do ácido biliar TUDCA no metabolismo glicêmico e energético de camundongos com Alzheimer e senis
• Beneficiário: Lucas Zangerolamo
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 18/06363-1 - Potencial terapêutico do GHRH e da metformina sobre a função da célula beta pancreática frente ao estresse de retículo endoplasmático e instalação do diabetes mellitus tipo 2
• Beneficiário: Helena Cristina de Lima Barbosa
• Modalidade de apoio: Auxílio à Pesquisa - Regular