Browsing by Author "Castro, Telma Cristina Aureliano"
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- Role of neuronal cholesterol in peripheric metabolic tissuesPublication . Castro, Telma Cristina Aureliano; Nóbrega, Clévio; Coelho, Ana Luísa De SousaThe brain possesses 20% of whole-body cholesterol, becoming the richest cholesterol organ in our body. Due to the Blood Brain Barrier, the cholesterol has its own way to synthesize and degrade cholesterol, in order to maintain its homeostasis. Cholesterol is synthesized through de novo synthesis in the brain and transported out of the brain in the form of oxysterols, more specifically 24-hydroxycholesterol (24-OHC). This process is acomplished through CYP46A1, a protein of the CYP450 family. Alterations in cholesterol homeostasis can lead to metabolic abnormalities, such as obesity, inflammation and insulin resistance. Previous studies in our laboratory showed that alterations in the expression of Cyp46A1 gene (more specifically silencing) with different diets, rich and poor in fat, had impacts in whole-body homeostasis. Taking these results into account, the main objective of this study was to evaluate the impact of modulation of Cyp46A1 gene in the main metabolic organs (liver, pancreas, and adipose tissue), through silencing and overexpressing CYP46A1 in the arcuate nucleus of the hypothalamus. This modulation was made in C57BL/6J mice fed with two distinct diets, one rich in fat (HF diet) and one poor in fat (CHOW diet). The data obtained from microscopy and tissue quantification made it possible to see the physiological changes resultant from the modulation of CYP46A1. It was possible the phenomenon BAT “whithening”, an increase in the size of Langerhans islets and lipidic hypertrophy. RT-qPCR was also realized to evaluate the mRNA levels of the different targets in the hypothalamus. The results obtained from RT-qPCR, showed that modulation of Cyp46A1 affected the mRNA levels of the different targets tested (POMC, NPY and TNF-alpha). All this data confirmed our hypothesis, that the modulation of CYP46A1 do alter the whole-body metabolism. Further studies must be conducted to continue this project, in order to investigate if this gene could be a target for genetic therapies.