Abstract
BackgroundA high-fat diet (HFD) can induce obesity and metabolic disorders that are closely associated with cognitive impairments, and the progression of several psychiatric disorders such as anxiety. We have previously demonstrated the anxiolytic-like effect of Gamma oryzanol (GORZ) in chronic restraint stressed mice.ObjectiveWe studied the neurochemical and molecular mechanisms that underlie the preventive effect of GORZ in HFD-induced anxiety-like behaviors, monoaminergic dysfunction, and inflammation.MethodsEight-week-old Institute of Cancer (ICR) male mice weighing 33–34 g were divided into the following groups and free-fed for 8 weeks: control (14% casein, AIN 93M); HFD; HFD + GORZ (0.5% GORZ). Body weight gain was checked weekly. The anxiolytic-like effects of GORZ were examined via open-field test (OFT) and elevated plus maze (EPM) test. Brain levels of monoamines [5-hydroxy tryptamine (5-HT), dopamine (DA), and norepinephrine (NE)] and their metabolites [5-hydroxyindole acetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG)], proinflammatory cytokines such as tumor necrosis factor-αα (Tnf-α) mRNA levels, and interleukin 1-β (Il-1β) mRNA levels in the cerebral cortex and amygdala were examined using high-performance liquid chromatography-electrochemical detection (HPLC-ECD), and real-time reverse transcription-polymerase chain reaction (RT-PCR), respectively.ResultsMice fed a HFD for eight weeks showed anxiety-like behaviors in association with HFD-induced body weight gain. GORZ potentially blocked HFD-induced anxiety-like behaviors via significant improvement of the primary behavioral parameters in behavioral tests, with a minor reduction in HFD-induced body weight gain. Furthermore, GORZ treatment significantly downregulated HFD-induced upregulation of dopamine levels in the brain's amygdala. Significant reduction of the relative mRNA expression of Tnf-α and Il-1 β was also observed in the amygdala of HFD + GORZ mice, compared to HFD mice.ConclusionsOur findings strongly suggest that 0.5% GORZ exerts anxiolytic-like effects, possibly through downregulation of dopamine, and via expression of proinflammatory cytokines Tnf-α and Il-1 β in the case of chronic HFD exposure.
Highlights
Long-term consumption of a high-fat diet (HFD) affects wholebody homeostasis and contributes to the development of weight gain/obesity and associated comorbidities, including depression and anxiety (Anderson et al, 2001; Petry et al, 2008; Gadalla, 2009; Mizunoya et al, 2013; Jacka et al, 2015)
A lack of significant changes in terms of important behavioral parameters recorded by the elevated plus maze (EPM) test in this preliminary experiment inspired us to formulate the present study design with three groups: control, HFD, and HFD + Gamma oryzanol (GORZ)
We previously demonstrated that 0.5% GORZ may act as a promising anxiolytic functional food in chronic restraint stressed mice, via regulation of central monoamine neurotransmitters in the amygdala (Akter et al, 2019)
Summary
Long-term consumption of a high-fat diet (HFD) affects wholebody homeostasis and contributes to the development of weight gain/obesity and associated comorbidities, including depression and anxiety (Anderson et al, 2001; Petry et al, 2008; Gadalla, 2009; Mizunoya et al, 2013; Jacka et al, 2015). It is welldocumented that HFD-induced behavioral impairments are closely associated with alteration of brain neurochemistry in a region-specific manner (Molteni et al, 2004; Sharma and Fulton, 2013), partially caused by a diet high in fat. A chronic (3 months) HFD altered striatal and mesolimbic dopamine (DA) signaling in rodents (Davis et al, 2008; Sharma and Fulton, 2013). Another animal study reported that chronic HFD consumption for 10 weeks targeted the cortex of mice, and caused emotional disturbances via DA dysfunction, characterized by increased DA turnover (Wakabayashi et al, 2015). We have previously demonstrated the anxiolytic-like effect of Gamma oryzanol (GORZ) in chronic restraint stressed mice
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