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Donepezil Prevents Inhibition of Cerebral Energetic Metabolism Without Altering Behavioral Parameters in Animal Model of Obesity

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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.

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Funding

This research was supported by grant from Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina (FAPESC) 2016TR2228. The funding sources were not involved in the conduction of the research, preparation of the article nor in the decision to submit the article for publication.

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  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

    Bianca Xavier de Farias, Ana Beatriz Costa, Nicole Alessandra Engel, Mariana Pereira de Souza Goldim, Cristini da Rosa Turatti, Anderson Cargnin-Cavalho, Jucélia Jeremias Fortunato, Fabricia Petronilho, Isabela Casagrande Jeremias & Gislaine Tezza Rezin

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  1. Bianca Xavier de Farias
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de Farias, B.X., Costa, A.B., Engel, N.A. et al. Donepezil Prevents Inhibition of Cerebral Energetic Metabolism Without Altering Behavioral Parameters in Animal Model of Obesity. Neurochem Res 45, 2487–2498 (2020). https://doi.org/10.1007/s11064-020-03107-x

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