P30 Cognitive and metabolic disorders induced by a high fat diet. Influence of exposition to chronic mild stress and effect of the treatment with metformin

Abstract

Introduction: Obesity is a serious health issue worldwide. Feeding habits and stress are among the environmental factors that contribute to its development. Additionally, it’s been described an association between obesity and cognitive function, being pointed as a risk factor for Alzheimer’s disease.

Objectives: To study the effect of a high-fat diet (HFD) consumption and the development of cognitive deficit. To evaluate whether the exposition to chronic mild stress aggravates the metabolic and/or cognitive disorders induced by the HFD. Furthermore, being the metformin (MET) a drug commonly used to treat diabetes, we will study its effects on behavior.

Methodology: One month old, Male C57Bl/6J mice were fed with a standard diet (SD; 2.96 kcal/g) or a high-fat diet (HFD; 4.37 kcal/g) during 28 weeks. At the 8th week of diet, animals were divided and a group of each diet were chronically exposed to random mild stressors (CMS). After 12 weeks of diet, a group of animals under each treatment were given MET (250 mg/kg*day). We studied the glucidic (basal glycemia, glucose tolerance, insulinemia) and lipidic metabolism (total cholesterol, HDL cholesterol, triglycerides) and we studied the behavior (learning, spatial memory, working memory).

Results: The HFD induced a higher body weight (p=0.0004) and glucose intolerance (p=0.0055). CMS exposure reduced body weight (p=0.0023) but increase basal glycemia (p=0.0335), glucose intolerance (p<0.0001) and insulin resistance (0=0.0023). No significant differences were found on lipidic metabolism. Memory studies indicate HFD, CMS and their sum induce cognitive impairment (Y-maze, SD+CMS p=0,0024, HFD
p=0,0002, HFD+CMS p=0,0034; Spatial object recognition SD+CMS p<0,0001, HFD p=0,0006, HFD+CMS: p=0,0002). Treatment with MET corrected the observed impariments in spatial and working memory induced both by HFD and CMS, without relevant effects being observed on weight nor glycemias.

Conclusions: HFD caused cognitive and metabolic disfunctions. CMS by itself causes cognitive impairment and worsens the metabolic disreglations caused by HFD. The treatment with MET prevents cognitive deficit both caused by HFD and CMS independently of its effect on the metabolism.