Energy homeostasis deregulation is attenuated by TUDCA treatment in streptozotocin‐induced Alzheimer’s disease mice model.
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2021
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Alzheimer’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.
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ZANGEROLAMO, L. et al. Energy homeostasis deregulation is attenuated by TUDCA treatment in streptozotocin‐induced Alzheimer’s disease mice model. Scientifc Reports, v. 11, 2021. Disponível em: <https://www.nature.com/articles/s41598-021-97624-6>. Acesso em: 11 out. 2022.