Decreasing unsaturation of dietary fats addresses a pathway-oriented profiling of brain lipids and lipid mediators that lead oxidative imbalance and inflammatory phenotypes

Growing evidences have shown that among the different genetic and environmental factors associated to biological aging, chronological age, and aging-associated disorders, diet plays a critical role. In this field, recent evidences demonstrate that dietary fat lead both metabolic diseases and risk for development of ‘cognitive decline’ or ‘cognitive impairment’. In particular, lipid metabolism modulates neuronal function and may signal nutrient status to influence metabolism in key peripherical tissues as liver. Especially, dietary fatty acids, as they act as signaling molecules responsible for inflammatory processes. But, even if clinical and epidemiological studies revealed that metabolic diseases and brain disorders might be related, the underlying pathology is multifactorial, making it hard to determine causal link. Common denominators of these metabolic and cognitive disorders are the oxidative imbalance and inflammatory response. On these bases, this work aims to study the effect of saturated and unsaturated dietary fats on the lipidomic and epilipidomic signatures of specific brain regions of animal models. Results demonstrated that the consumption of high saturated fat provokes a pro-inflammatory phenotype linked to an increase of lipid oxidation in brain cortex and cerebellum of rodents. Moreover, the consumption of saturated diets lead a high oxidative stress sited in specific brain regions, demonstrating that cerebellum characterized by a major unsaturated fatty acid proportion, is a major target of oxidative stress lead by unhealthy diets. A noteworthy result is that the dietary fat supplementation during four months lead to specific inflammatory phenotypes which can be counteracted by marine lipids having high contents of EPA and DHA. Therefore, increased dietary lipid unsaturation resulted in a significant inhibition of the state of chronic inflammation and oxidative stress in brain regions associated to the consumption of unhealthy diets. These positiv