Pathways of polyunsaturated fatty acid utilization: Implications for brain function in neuropsychiatric health and disease

Abstract

Essential polyunsaturated fatty acids (PUFAs) have profound effects on brain development and function. Abnormalities of PUFA status have been implicated in neuropsychiatric diseases such as major depression, bipolar disorder, schizophrenia, Alzheimer’s disease, and attention deficit hyperactivity disorder. Pathophysiologic mechanisms could involve not only suboptimal PUFA intake, but also metabolic and genetic abnormalities, defective hepatic metabolism, and problems with diffusion and transport. This article provides an overview of physiologic factors regulating PUFA utilization, highlighting their relevance to neuropsychiatric disease.

Fatty acid binding proteins have the potential to channel dietary fatty acids into enterocyte nuclei

“…In addition, fabp1b.1 and fabp1b.2 transcripts were found in liver and brain, respectively, supporting the hypothesis that these tandem-duplicated genes have a differential, tissue-specifi c function. The relatively high levels of fabp1b.2 in brain may be attributable to ligand preferences because it is known that polyunsaturated FAs are highly abundant in the central nervous system ( 66,67 ). Whole-mount in situ hybridization demonstrated high transcript levels of fabp1b ( fabp1b.1 plus fabp1b.2 ) and fabp2 in the anterior intestine, but no mRNAs were detected in the posterior drugs and xenobiotics, controlling their uptake and intracellular transport (i.e., FABPs act as chaperones) (13)(14)(15)(16)(17)57 ).…”

B-Vitamins and One-Carbon Metabolism

“…Studies involving populations with lower baseline folate status in general support the role of folate in cognitive dysfunction [160][161][162] and cognitive decline [163,164], whereas those in countries with food fortification policies and thus overall higher mean concentrations of folate, are generally less supportive for a role in cognitive dysfunction [165,166], cognitive decline [167][168][169] or dementia [170]. Similarly, a number of large cohort studies have associated low vitamin B12 status (using more sensitive biomarkers of status including MMA and HoloTC) with cognitive dysfunction [160,166,171] and cognitive decline [162,172,173] in older people. However, the evidence for B12 is less convincing, and one meta-analysis has shown no association of vitamin B12 with cognitive decline or dementia (n = 14,325) [174].…”

“…The presence of Cbl inside the human gut is not a sufficient amount in terms of a daily intake, since it cannot be absorbed through the specific transport that requires binding to the transporters. In addition, 98% of corrinoid compounds synthesized by the microbiota found in human feces appear to be inactive [171].…”

Correlation between intake of omega-3 fatty acids and depressive and anxiety symptoms during pregnancy

“…An inverse association between a per capita intake of fish and an annual prevalence of depression was observed in the last 15 years (Grosso et al, 2014),which led to propose that dietary deficiency of ω-3FA (measured as plasmatic, erythrocyte, and brain concentrations) is associated with higher depression, both in the perinatal period (Hibbeln, 2002;Markhus et al, 2013) and in other stages of life (Hoffmire, Block, Thevenet-Morrison, & van Wijngaarden, 2012;Grosso et al, 2014;Su, Matsuoka, & Pae, 2015).There is a relation between the intake of ω-3FA and prenatal AS in animal and human models (Mizunoya et al, 2013;Vaz et al, 2013;Liu et al, 2015;Su et al, 2015).…”

“…During the last trimester of pregnancy 67 mg/d of DHA are transferred to the fetus for the growth and development of its brain and retina. About 50% to 60% of the dry weight of an adult brain is composed of lipids, of which 20% corresponds to DHA (Liu, Green, Mann, Rapoport, & Sublette, 2015). Thus, if the intake of ω-3FA by the mother is insufficient, it is common that pregnancy depletes the mother's stock of cerebral and erythrocyte ω-3FA (Morse, 2012).…”