Diet-Derived Fatty Acids, Brain Inflammation, and Mental Health

Abstract

Western societies experienced drastic changes in eating habits during the past century. The modern nutritional profile, typically rich in saturated fats and refined sugars, is recognized as a major contributing factor, along with reduced physical activity, to the current epidemics of metabolic disorders, notably obesity and diabetes. Alongside these conditions, recent years have witnessed a gradual and significant increase in prevalence of brain diseases, particularly mood disorders. While substantial clinical/epidemiological evidence supports a correlation between metabolic and neuropsychiatric disorders, the mechanisms of pathogenesis in the latter are often multifactorial and causal links have been hard to establish. Neuroinflammation stands out as a hallmark feature of brain disorders that may be linked to peripheral metabolic dyshomeostasis caused by an unhealthy diet. Dietary fatty acids are of particular interest, as they may play a dual role, both as a component of high-calorie obesogenic diets and as signaling molecules involved in inflammatory responses. Here, we review current literature connecting diet-related nutritional imbalance and neuropsychiatric disorders, focusing on the role of dietary fatty acids as signaling molecules directly relevant to inflammatory processes and to neuronal function.

Multiple Pathways Involved in Palmitic Acid-Induced Toxicity: A System Biology Approach

“…Additionally, both palmitic acid and stearic acid were shown to increase the secretion of Aβ amyloid peptide in an AD cellular model (Amtul et al, 2011). Recent studies in human populations also point an inverse correlation between clinical obesity and neuroinflammation (Barnard et al, 2014;Reichelt et al, 2017;Melo et al, 2019), suggesting that long-term consumption of high fat diets is associated with pathological mechanisms in the brain (Melo et al, 2019). Moreover, the increase of saturated free fatty acids during metabolic inflammation activates IKKβ kinase and its downstream effector NF-κβ, which in turn impairs leptin and insulin hormonal signaling and triggers the production and release of reactive oxygen species (ROS) and pro-inflammatory cytokines like TNF-α and IL-6 from glial cells (Purkayastha and Cai, 2013).…”

Dietary n-6/n-3 Ratio Influences Brain Fatty Acid Composition in Adult Rats

“…There are important links between diet and psychopathology [1]. For instance, diets characterized by high n-6/n-3 poly-unsaturated fatty acid (PUFA) ratios have been linked to a variety of affective, cognitive and behavioral deficits [2,3]. Moreover, patients suffering from conditions ranging from Alzheimer's to major depression display lower n-3 PUFA and higher n-6 PUFA levels in brain and plasma [4,5].…”

Metabolic Endotoxemia: A Potential Underlying Mechanism of the Relationship between Dietary Fat Intake and Risk for Cognitive Impairments in Humans?

“…(4) Conclusions: A fat-rich diet has the capability to provide significant increases in circulating endotoxins, which highlights nutritional strategies as a promising area for future research on inflammatory-associated diseases. The role of endotoxemia in cognitive disorders and dementia remains unclear and deserves further investigation.Nutrients 2019, 11, 1887 2 of 23 the plant-based Mediterranean diet, on age-related cognitive impairments, whether they are due to degenerative or vascular origin [5][6][7][8].Conversely, the Western diet, characterized among other factors by a high intake of saturated and trans fatty acids, has been associated with an increased risk of developing dementia [5,7]. Moreover, adopting this fat-rich dietary pattern can lead to metabolic disorders such as obesity or Type 2 Diabetes Mellitus (T2DM), these latter being associated with a higher risk of developing dementia in later life [9,10].Nutritional strategies represent a promising area to prevent neurocognitive impairments and subsequent dementia.…”

“…Nutrients 2019, 11, 1887 2 of 23 the plant-based Mediterranean diet, on age-related cognitive impairments, whether they are due to degenerative or vascular origin [5][6][7][8].…”