(-)-Epicatechin mitigates anxiety-related behavior in a mouse model of high fat diet-induced obesity

Kang, Jiye, Wang, Ziwei, Cremonini, Eleonora, Gall, Gwenaelle Le ORCID: https://orcid.org/0000-0002-1379-2196, Pontifex, Matthew G., Muller, Michael ORCID: https://orcid.org/0000-0002-5930-9905, Vauzour, David ORCID: https://orcid.org/0000-0001-5952-8756 and Oteiza, Patricia I. (2022) (-)-Epicatechin mitigates anxiety-related behavior in a mouse model of high fat diet-induced obesity. Journal of Nutritional Biochemistry. ISSN 0955-2863

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Mounting evidence demonstrates that consumption of high fat diet (HFD) and subsequent development of obesity leads to alterations in cognition and mood. While obesity can affect brain function, consumption of select dietary bioactives may help prevent obesity-related cognitive decline. This study investigated the capacity of the dietary flavonoid (-)-epicatechin (EC) to mitigate HFD-induced obesity-associated alterations in memory and mood. Healthy 8-week old male C57BL/6J mice were maintained on either a control diet (10 kCal% from fat) or a HFD (45 kCal% from fat) and were supplemented with EC at 2 or 20 mg/kg body weight (B.W.) for a 24 week period. Between week 20 and 22, anxiety-related behavior, recognition memory, and spatial memory were measured. Underlying mechanisms were assessed by measuring the expression of selected genes in the hippocampus and by 16S rRNA sequencing and metabolomic analysis of the gut microbiota. 24 weeks of HFD feeding resulted in obesity, which was not affected by EC supplementation. HFD-associated increase in anxiety-related behavior was mitigated by EC in a dose-response manner and was accompanied by increased hippocampal brain-derived neurotrophic factor, as well as partial or full restoration of glucocorticoid receptor, mineralocorticoid receptor and 11β-HSD1 expression. Higher EC dosage (20 mg/kg B.W.) also restored aberrant Lactobacillus and Enterobacter abundance altered by HFD and/or the associated obesity. Together, these results demonstrate how EC mitigates anxiety-related behaviors, revealing a connection between BDNF- and glucocorticoids-mediated signaling . Our findings link changes in the hippocampus and the gut microbiota in a context of HFD-induced obesity and anxiety.

Item Type: Article
Uncontrolled Keywords: sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 21 Sep 2022 10:30
Last Modified: 26 Sep 2022 06:04
URI: https://ueaeprints.uea.ac.uk/id/eprint/88549
DOI: 10.1016/j.jnutbio.2022.109158

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