Chronic psychological stress and high-fat high-fructose diet disrupt metabolic and inflammatory gene networks in the brain, liver, and gut and promote behavioral deficits in mice

Chronic psychological stress and high-fat high-fructose diet disrupt metabolic and inflammatory gene networks in the brain, liver, and gut and promote behavioral deficits in mice

Author Rodrigues, Maria Elizabeth de Sousa Autor UNIFESP Google Scholar
Bekhbat, Mandakh Google Scholar
Houser, Madelyn C. Google Scholar
Chang, Jianjun Google Scholar
Walker, Douglas I. Google Scholar
Jones, Dean P. Google Scholar
Nascimento, Claudia Maria da Penha Oller do Autor UNIFESP Google Scholar
Barnum, Christopher J. Google Scholar
Tansey, Malu G. Google Scholar
Abstract The mechanisms underlying the association between chronic psychological stress, development of metabolic syndrome (MetS), and behavioral impairment in obesity are poorly understood. The aim of the present study was to assess the effects of mild chronic psychological stress on metabolic, inflammatory, and behavioral profiles in a mouse model of diet-induced obesity. We hypothesized that (1) high-fat high-fructose diet (HFHF) and psychological stress would synergize to mediate the impact of inflammation on the central nervous system in the presence of behavioral dysfunction, and that (2) HFHF and stress interactions would impact insulin and lipid metabolism. C57BI/6 male mice underwent a combination of HFHF and two weeks of chronic psychological stress. MetS-related conditions were assessed using untargeted plasma metabolomics, and structural and immune changes in the gut and liver were evaluated. Inflammation was measured in plasma, liver, gut, and brain. Our results show a complex interplay of diet and stress on gut alterations, energetic homeostasis, lipid metabolism, and plasma insulin levels. Psychological stress and HFHF diet promoted changes in intestinal tight junctions proteins and increases in insulin resistance and plasma cholesterol, and impacted the RNA expression of inflammatory factors in the hippocampus. Stress promoted an adaptive anti-inflammatory profile in the hippocampus that was abolished by diet treatment. HFHF increased hippocampal and hepatic Lcn2 mRNA expression as well as LCN2 plasma levels. Behavioral changes were associated with HFHF and stress. Collectively, these results suggest that diet and stress as pervasive factors exacerbate MetS-related conditions through an inflammatory mechanism that ultimately can impact behavior. This rodent model may prove useful for identification of possible biomarkers and therapeutic targets to treat metabolic syndrome and mood disorders. (C) 2016 Elsevier Inc. All rights reserved.
Keywords Predatory stress
Depression
Metabolic syndrome
Insulin
Cholesterol
Lipocalin-2
Metabolomics
Biliverdin
xmlui.dri2xhtml.METS-1.0.item-coverage San Diego
Language English
Sponsor Emory Multiplexed Immunoassay Core (EMIC)
Emory University School of Medicine
National Center for Advancing Translational Sciences of the National Institutes of Health
National Institutes of Health (NIH)/National Institute of Mental Health (NIMH)
Grant number National Center for Advancing Translational Sciences of the National Institutes of Health: UL1TR000454
NIH/NIMHS: 1R43MH105048-01A1
Date 2017
Published in Brain Behavior And Immunity. San Diego, v. 59, p. 158-172, 2017.
ISSN 0889-1591 (Sherpa/Romeo, impact factor)
Publisher Academic Press Inc Elsevier Science
Extent 158-172
Origin http://dx.doi.org/10.1016/j.bbi.2016.08.021
Access rights Closed access
Type Article
Web of Science ID WOS:000390618700016
URI https://repositorio.unifesp.br/handle/11600/56512

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