Donepezil Prevents Inhibition of Cerebral Energetic Metabolism Without Altering Behavioral Parameters in Animal Model of
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ORIGINAL PAPER
Donepezil Prevents Inhibition of Cerebral Energetic Metabolism Without Altering Behavioral Parameters in Animal Model of Obesity Bianca Xavier de Farias1 · Ana Beatriz Costa1 · Nicole Alessandra Engel1 · Mariana Pereira de Souza Goldim1 · Cristini da Rosa Turatti1 · Anderson Cargnin‑Cavalho1 · Jucélia Jeremias Fortunato1 · Fabricia Petronilho1 · Isabela Casagrande Jeremias1 · Gislaine Tezza Rezin1 Received: 5 March 2020 / Revised: 13 July 2020 / Accepted: 29 July 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Obesity is characterized by chronic inflammation of low grade. The cholinergic anti-inflammatory pathway favors the reduction of the inflammatory response. In this work the effect of stimulation of the cholinergic anti-inflammatory pathway on SHIRPA behavioral test and mitochondrial respiratory chain activity in obese mice was evaluated. The animals were paired in four groups: saline + control diet; donepezil + control diet; saline + high-fat diet and donepezil + high-fat diet. 5 mg/kg/day orally of donepezil or saline were given 7 days before the beginning of the diet until completing 11 weeks of the experiment. Food intake and body weight were measured. At the end of the experiment the animals were submitted to the SHIRPA behavioral test, soon after they were killed by decapitation, the open abdominal cavity and the mesenteric fat were removed. The hypothalamus, hippocampus, prefrontal cortex, and striatum were removed for evaluation of the mitochondrial respiratory chain. It can be observed that donepezil prevented weight gain and food consumption, as well as a tendency to prevent the accumulation of mesenteric fat in obese animals. There was no behavioral change in obese animals, nor did the influence of donepezil on these parameters. On the other hand, donepezil did not prevent inhibition of complex I activity, prevented the inhibition of complex II, and showed a tendency to prevent IV complex activity inhibited in obesity. With these results it can be concluded that the activation of the cholinergic anti-inflammatory pathway is promising for the alterations found in obesity. Keywords Obesity · Cholinergic anti-inflammatory pathway · Donepezil · Central nervous system · Energy metabolism
Introduction Obesity is a serious health problem defined by the World Health Organization (WHO) as an excessive accumulation of fat that can bring harm to the individual [1, 2]. It is an important risk factor for triggering other chronic diseases, such as type 2 diabetes mellitus, cardiovascular diseases, non-alcoholic hepatic steatosis, respiratory diseases and cancer [1, 3]. The number of obese people has almost tripled since 1975, and in 2016, 39% of people over 18 years were overweight and 13% were obese [1].
* Gislaine Tezza Rezin [email protected] 1
Laboratório de Neurobiologia de Processos Inflamatórios e Metabólicos, Universidade do Sul de Santa Catarina, Programa de Pós-Graduação em Ciências da Saúde, Tubarão, Santa Catarina, Brasil
Obesity is a mult
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