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Identification of central mechanisms underlying statin-induced changes in consummatory behaviour in rats

Simvastatin is a cholesterol lowering statin whose adverse effects include an increase in appetite and, consequently, obesity. This is counterproductive to the otherwise beneficial outcomes of simvastatin on metabolic and cardiovascular health. The mechanisms underlying simvastatin-induced hyperphagia are unknown. This thesis investigated by using a laboratory rat model whether central mechanisms contribute to simvastatin-induced increase in appetite. First, the effect of intracerebroventricularly (ICV) administered simvastatin on the energy-driven intake of ‘bland’ chow, and on reward-motivated consumption of palatable solutions, was determined. The data indicate that ICV simvastatin moderately increases ingestion of energy-dense chow, but it does not affect consumption of calorie-dilute and non-caloric palatable sucrose or saccharin solutions. It suggests that simvastatin acting directly at the brain level elevates intake of energy, while being ineffective in stimulating eating for reward. Surprisingly, rats injected ICV with this statin consume also significantly more water after water deprivation, which points to a relationship between centrally acting simvastatin and thirst-related processing. In the second part of this project, the effect of the orexigenic dose of ICV simvastatin on neuronal activation in consumption-related hypothalamic sites was investigated. Simvastatin elevated c-Fos immunoreactivity, which serves as a marker of neuronal activation, in the arcuate and paraventricular nuclei, two sites that have a profound influence on the regulation of energy intake and energy balance, as well as affect water balance. It can be concluded that simvastatin increases intake of energy and of water, and that it likely exerts its action through the hypothalamic paraventricular and arcuate nuclei.
Type of thesis
Isgrove, K. (2017). Identification of central mechanisms underlying statin-induced changes in consummatory behaviour in rats (Thesis, Master of Science (Research) (MSc(Research))). University of Waikato, Hamilton, New Zealand. Retrieved from https://hdl.handle.net/10289/11331
University of Waikato
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