title: The saturated fatty acid, palmitic acid, induces anxiety-like behavior in mice.
abstract: OBJECTIVE
  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 24h 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.
authors.affiliation: Division of Nutritional Sciences, University of Illinois, Urbana IL, USA.
authors.forename: Morgan L
authors.initials: ML
authors.lastname: Moon
authors.affiliation: Department of Pathology, Program in Integrative Immunology and Behavior, University of Illinois, Urbana IL, USA.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Joesting
authors.affiliation: Department of Animal Sciences, University of Illinois, Urbana IL, USA.
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Lawson
authors.affiliation: Division of Nutritional Sciences, University of Illinois, Urbana IL, USA.
authors.forename: Gabriel S
authors.initials: GS
authors.lastname: Chiu
authors.affiliation: Department of Pathology, Program in Integrative Immunology and Behavior, University of Illinois, Urbana IL, USA.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Blevins
authors.affiliation: Department of Pathology, Program in Integrative Immunology and Behavior, University of Illinois, Urbana IL, USA.
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Kwakwa
authors.affiliation: Division of Nutritional Sciences, University of Illinois, Urbana IL, USA; Department of Pathology, Program in Integrative Immunology and Behavior, University of Illinois, Urbana IL, USA; Department of Animal Sciences, University of Illinois, Urbana IL, USA. Electronic address: freun@illinois.edu.
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Freund
mesh_terms: D051701:Activating Transcription Factor 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000097:blood / Q000209:etiology*; D001522:Behavior, Animal; D002540:Cerebral Cortex / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D005230:Fatty Acids, Nonesterified / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D006963:Hyperphagia / Q000378:metabolism / Q000503:physiopathology; D007274:Injections, Intraperitoneal; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D019308:Palmitic Acid / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood
chemical_list: C081452:Atf4 protein, mouse; D005230:Fatty Acids, Nonesterified; D009419:Nerve Tissue Proteins; D051701:Activating Transcription Factor 4; D019308:Palmitic Acid; D006897:Hydroxyindoleacetic Acid
keywords: Anxiety; Free fatty acid; Palmitic acid