Obesity and Alzheimer´s disease: unraveling the impact of chronic consumption of high-fat or high-sucrose diets on neurodegeneration and mitochondrial dysfunction.

Abstract

The global incidence of obesity and metabolic disorders has been associated with alterations in the central nervous system, prominently featuring increased oxidative stress and heightened production of amyloid beta peptide (AB), stemming from mitochondrial dysregulations, which potentially contribute to the onset of neurodegenerative disorders like Alzheimer disease. In this study, we sought to ascertain whether chronic consumption of unbalanced diets by rats leads to elevated AB production and accumulation in brain structures, driving neuronal damage and mitochondrial dysfunction. Male Wistar rats were fed with unbalanced diets rich in sucrose or lard for 12 months. Subsequently, we evaluated zoometric and biochemical parameters, including glucose tolerance, serum cholesterol, and triglycerides, alongside spatial memory. Additionally, AB accumulation, oxidative stress markers, and mitochondrial respiratory chain activity were analyzed in mitochondria and homogenates from the hippocampus and cerebral cortex. In our results, both dietary interventions induced abdominal obesity and spatial memory deterioration, associated to glucose metabolism disturbance, mitochondrial dysfunction, and increased oxidative stress. Nevertheless, AB accumulation was evident only in the mitochondria of rats fed with the sucrose-enriched diet. With these findings, we show that, although excessive consumption of fat or sucrose drives to obesity, only the last could potentially bridge the gap between obesity and neurodegenerative pathogenesis, thereby highlighting the relevance of lifestyle and diet quality, bringing a way to develop preventive strategies.