Life Sci. , 2023, Dec 18;337:122356.

Important roles of linoleic acid and α-linolenic acid in regulating cognitive impairment and neuropsychiatric issues in metabolic-related dementia.

Kim OY Song J.


Metabolic syndrome (MetS), which is characterized by insulin resistance, high blood glucose, obesity, and dyslipidemia, is known to increase the risk of dementia accompanied by memory loss and depression. The direct pathways and specific mechanisms in the central nervous system (CNS) for addressing fatty acid imbalances in MetS have not yet been fully elucidated. Among polyunsaturated acids, linoleic acid (LA, n6-PUFA) and α-linolenic acid (ALA, n3-PUFA), which are two essential fatty acids that should be provided by food sources (e.g., vegetable oils and seeds), have been reported to regulate various cellular mechanisms including apoptosis, inflammatory responses, mitochondrial biogenesis, and insulin signaling. Furthermore, inadequate intake of LA and ALA is reported to be involved in neuropathology and neuropsychiatric diseases as well as imbalanced metabolic conditions. Herein, we review the roles of LA and ALA on metabolic-related dementia focusing on insulin resistance, dyslipidemia, synaptic plasticity, cognitive function, and neuropsychiatric issues. This review suggests that LA and ALA are important fatty acids for concurrent treatment of both MetS and neurological problems. Highlights: LA and ALA attenuate neuroinflammation by modulating inflammatory signaling; LA and ALA ameliorate dyslipidemia by increasing HDL-C and regulating lipid metabolism; LA and ALA enhance neuropsychiatric issues such as depression by modulating neurotransmitter secretion; LA and ALA attenuate AD pathologies including synaptic dysfunction.

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