Banca de DEFESA: Wembley Rodrigues Vilela

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : Wembley Rodrigues Vilela
DATE: 18/09/2024
TIME: 14:00
LOCAL: Plataforma TEAMS - online
TITLE:

Effect of lipid overload on neural bioenergetics: In vivo and in vitro approaches.

 

KEY WORDS:

metabolic dysfunction, mitochondria, cognition, hippocampus, microglia, palmitate.

PAGES: 98
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

The excessive intake of diets rich in saturated fats is a risk factor for the development of metabolic changes, particularly affecting the brain, as cognitive decline is observed in animal models of obesity and in obese humans. We hypothesized that mitochondrial physiology of neural cells are affected by lipid overload and evaluated this hypothesis in an experimental model of metabolic dysfunction and in microglial cells. For in vivo experiments, 8-week-old male Wistar rats received a control diet or a high-fat diet (HFD) associated with L-NAME in their drinking water. HFD+LNAME induced obesity, hypertension and increased serum cholesterol. This metabolic dysfunction was associated with impairment in the spatial learning phase of the Morris Water Maze. Mitochondrial dysfunction in the hippocampus was evidenced by a decrease in oxygen (O2) consumption related to ATP production, a tendency to decrease maximum mitochondrial capacity and an increase in the expression of the OPA1 protein in the hippocampus of rats exposed to HFD+L-NAME, without changes in other proteins related to mitochondrial dynamics. Mitochondrial function and calcium uptake rate and retention capacity in the neocortex were not impaired in rats exposed to HFD+ L-NAME. For in vitro experiments, BV2 microglial cells were cultured in low glucose (LG), or high glucose (HG), (5.5 and 25mM, respectively), and stimulated for 24h with palmitate (100 and 200µM), in order to induce metabolic dysfunction. Exposure to palmitate decreased cell viability in HG conditions, compared to LG. Effects of palmitate treatment were observed on CD68, Il-1β and IL-10 genes, and an effect of palmitate was also observed on lipid metabolism genes, without changes in glucose metabolism ones. The HG medium induced an increase in the values of oxidative respiration and glycolytic flux in relation to the LG, and palmitate treatment reduced the values of both oxidative and glycolytic fluxes. Co-treating the cells with the short-chain fatty acid butyrate was not sufficient to prevent the changes in mitochondrial function induced by palmitate. In primary microglial culture, palmitate did not induce changes in the mitochondrial area or in the metabolism of synaptosomes. Our results indicate a greater propensity of BV2 cells to suffer the viability-toxic effects of palmitate when cultured in HG. Palmitate was able to increase the expression of genes related to inflammation and lipid metabolism. Furthermore, the HG medium itself increased metabolic flux, which was reduced by palmitate, regardless of the culture medium used.

COMMITTEE MEMBERS:
Interna - 1208515 - ANDREA QUEIROZ MARANHAO
Presidente - 2343068 - ANDREZA FABRO DE BEM
Externa à Instituição - DAIANE FÁTIMA ENGEL - UFOP
Interna - 2862542 - KELLY GRACE MAGALHAES
Externo à Instituição - MYCHAEL VINICIUS DA COSTA LOURENÇO - UFRJ