The saturated fatty acid, palmitic acid, induces anxiety-like behavior in mice

• Published in: Metabolism, clinical and experimental Vol. 63; no. 9; pp. 1131 - 1140
• Main Authors: Moon, Morgan L, Joesting, Jennifer J, Lawson, Marcus A, Chiu, Gabriel S, Blevins, Neil A, Kwakwa, Kristin A, Freund, Gregory G
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.09.2014; Elsevier
• Subjects: Activating Transcription Factor 4 - antagonists & inhibitors; Activating Transcription Factor 4 - genetics; Activating Transcription Factor 4 - metabolism; Amygdala - metabolism; Animals; Anxiety; Anxiety - blood; Anxiety - etiology; Behavior, Animal; Biological and medical sciences; Cerebral Cortex - metabolism; Diet, High-Fat - adverse effects; Endocrinology & Metabolism; Fatty Acids, Nonesterified - administration & dosage; Fatty Acids, Nonesterified - adverse effects; Fatty Acids, Nonesterified - blood; Feeding. Feeding behavior; Free fatty acid; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Hippocampus - metabolism; Hydroxyindoleacetic Acid - metabolism; Hyperphagia - metabolism; Hyperphagia - physiopathology; Injections, Intraperitoneal; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor Activity; Nerve Tissue Proteins - antagonists & inhibitors; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurons - metabolism; Palmitic acid; Palmitic Acid - administration & dosage; Palmitic Acid - adverse effects; Palmitic Acid - blood; Vertebrates: anatomy and physiology, studies on body, several organs or systems; FFA; norepinephrine; HFD; 3,4-dihydroxyphenylacetic acid; homovanillic acid; free fatty acids; Free fatty acid; Palmitic acid; MyD88; serotonin; UPR; Anxiety; TLR; interleukin; Toll-like receptor; knockout; IL; DOPAC; KO; T2D; NME; myeloid differentiation primary response gene; normetanephrine; unfolded protein response; 5-hydroxyindoleacetic acid; HVA; type 2 diabetes; 5-HIAA; high-fat diet; NE; 5-HT; DA; dopamine; Affect affectivity; Vertebrata; Mammalia; Mouse; Saturated fatty acid; Animal; Rodentia; Lipids; Behavior; Endocrinology
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2014.06.002

Abstract Objectives Excess fat in the diet can impact neuropsychiatric functions by negatively affecting cognition, mood and anxiety. We sought to show that the free fatty acid (FFA), palmitic acid, can cause adverse biobehaviors in mice that last beyond an acute elevation in plasma FFAs. Methods Mice were administered palmitic acid or vehicle as a single intraperitoneal (IP) injection. Biobehaviors were profiled 2 and 24 h after palmitic acid treatment. Quantification of dopamine (DA), norepinephrine (NE), serotonin (5-HT) and their major metabolites was performed in cortex, hippocampus and amygdala. FFA concentration was determined in plasma. Relative fold change in mRNA expression of unfolded protein response (UPR)-associated genes was determined in brain regions. Results In a dose-dependent fashion, palmitic acid rapidly reduced mouse locomotor activity by a mechanism that did not rely on TLR4, MyD88, IL-1, IL-6 or TNFα but was dependent on fatty acid chain length. Twenty-four hours after palmitic acid administration mice exhibited anxiety-like behavior without impairment in locomotion, food intake, depressive-like behavior or spatial memory. Additionally, the serotonin metabolite 5-HIAA was increased by 33% in the amygdala 24 h after palmitic acid treatment. Conclusions Palmitic acid induces anxiety-like behavior in mice while increasing amygdala-based serotonin metabolism. These effects occur at a time point when plasma FFA levels are no longer elevated.