Early exposure to a high fat diet produces metabolic and behavioral alterations associated to hippocampal neuroinflammation and impaired neurogenesis in C57BL/6 mice

VINUESA A; POMILIO C; BEAUQUIS J; SARAVIA F

Rio de Janeiro

Congreso; IBRO meeting; 2015

IBRO

The incidence of metabolic disorders including obesity, T2 diabetes and metabolic syndrome has seriously increased in the last decades. These morbidities constitute major risk factors for neurodegenerative disorders such as Alzheimer?s disease (AD), which has a growing impact in modern societies. Several studies report that insulin resistance, impaired insulin signaling and inflammation promote cognitive impairment playing an essential role in the development of AD pathology.AimsEstablish a murine model of high fat diet (HFD) induced moderate obesity.Assess the behavioral profile of HFD mice, characterize central alterations in limbic structures and analyze a potential association between them.Explore the molecular mechanisms involved in the interaction of both metabolic and neurodegenerative pathologies.MethodsC57BL/6 male mice were given either a control diet CD (12% Kcal from fat) or HFD (45% kcal from fat) during 18 weeks since a week post weaning. Body weight and food consumption was registered weekly and behavioral tests were performed by the end of the treatment, from the 15th week onwards in a suitable room within housing facilities.Trunk blood, brain, liver and pancreas where rapidly extracted after decapitation. Determination of lipids, glucose in plasma and pancreatic insulin was/ were? done after a 6 hour fast.Results and ConclusionsExposure to HFD produces metabolic alterations along with changes in behavior and central parameters. HFD mice present elevated insulin levels, dyslipidemia and greater levels of lipids in hepatocytes. Alterations in the behavioral profile of the HFD group are shown by a set of different tests. A general alteration seen in the impediment in the Nest Building Test; deficiencies in short and mid-term spatial memory assessed with the Novel Object Localization Recognition test and Y maze test, respectively; anxious behavior in the Elevated Plus Maze and depressive- like behavior in the Tail Suspension Test. Among the central parameters, we found that the neurogenic ability is altered in HFD mice. There is decreased proliferation of neural progenitors in the dentate gyrus of the hippocampus (a lower number of Ki67+ cells). Differentiation seems also altered in HFD mice a lower number of immature neurons (DCX+ cells) were found in the dentate gyrus of the dorsal hippocampus.. Moreover, a greater density of microglial cells were found in the hilus of HDF mice, identified as Iba1 + cells These cells exhibited an enlarged soma, in the the hilus and stratum radiatum, evidencing a potential inflammatory response in the hippocampus due to HFD. Additionally, we also found an increased neural activity in the amygdala, structure mostly related to emotions, mood and fear, shown by a larger number of c-Fos+ nuclei.Our data portrays a set of alterations in behavior and central parameters as a consequence of an early exposure to a high fat diet,