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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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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]
Número total de Autores: 8
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
Número total de Afiliações: 2
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
Linha de fomento: 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
Linha de fomento: 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
Linha de fomento: Auxílio à Pesquisa - Regular