2019 Research Forum

California State University Bakersfield - CSUB

Is a High Fat Diet Always Bad? The Effects of a Low and High Fat Diet and the Selective Serotonin Reuptake Inhibitor, Fluoxetine (Prozac), in an Animal Model of Depress ion Morgan Musquez, Alam Alvarado, Leticia Herrera, Irene Cabanillas & Isabel C. Sumaya Behavioral Neuroscience Laboratory, Department of Psychology, California State University, Bakersfield, CA.

Background

Diets

Aims

Procedure & Design

Major depressive disorder is one of the most prevalent psychiatric disorders world-wide. In the United States alone over 16 million adults will suffer a major depressive episode during the year (SAMHSA, U.S. Department of HHS, 2016). A significant public health issue, depression is now the second leading cause of disability world-wide contributing greatly to the burden of disease (Ferrari et al., 2013). Another health issue affecting even more adults in the US is the growing number of individuals that are overweight. In the United States alone, an estimated 160 million adults are either obese or overweight (CDC, 2014). In making a link between the two, the Center for Disease Control (CDC, 2014), reports that nearly 43% of adults with depression are obese. As a result, depression has been associated with overeating, and poor food choices that have been linked to the intake of high fat. The overwhelming consensus in both human and animal studies is that high fat intake leads to negative outcomes and a risk factor for many health concerns including diabetes, heart disease, and stroke. Counterintuitive, there is emerging preclinical evidence that a high fat diet may not always have negative effects in the context of the psychological domain. For instance, investigating the interaction between a high fat diet and the commonly prescribed anti-depressant, fluoxetine (Prozac), Sumaya et al., (2016) showed anti-depressive effects of high fat in an animal model of depression, the Forced Swim Test. Rats were fed a high fat diet for seven days and showed less learned helplessness, a key symptom of depression found in humans. In Sumaya et al., a 32% isocaloric fat diet was used. The aim of the present study was to further investigate the previously reported anti-depressive effects of a high fat diet and to provide an animal model of food intake more closely mimicking that found in humans, a 45% non-isocaloric fat diet (Western Diet). Additionally, previous studies have used as a control diet, standard chow containing different amounts of macronutrients. To rule out the effects of macronutrients (Carbohydrates and Proteins), used in the current experiment was a low-fat diet (10% fat) with the exact macronutrients as the high-fat. As in Sumaya et al., also tested was treatment with the selective serotonin reuptake inhibitor, fluoxetine.

Summary and Conclusions

Results

Conclusions

Although high fat diets have been associated with many negative outcomes, high fat intake may serve as a protective agent in depression. Although low fat diets have been associated with many positive outcomes, low fat diet may be detrimental for depression.

Method

Rats. The subjects used in the experiment were male Sprague-Dawley rats (N=36, 126-150g) (Charles River, Inc., USA). Rats were maintained in a 12L/12D cycle with lights on at 0600 hrs and fed standard lab chow ad libitum for the period prior to experimentation. The animals were cared for and treated in accordance with the policies and regulations set forth by the National Institutes of Health and the protocol was approved by the Institutional Animal Care and Use Committee at California State University, Bakersfield.

Independentsamples t -tesstshowedno differencesbetween the two groupson weight (low fat = 246g+ 3.91g vs high fat = 225g+ 3.78g)andonmuscle strength (low fat = 3.36 sec + .66 sec vs high fat= 3.48 sec+ .59 sec). Accordingly,muscle strengthandweight were ruledout as having an impacton swim behavior.

Hanging Wire Test

Future Directions

• Rule our the effect of carbohydrates as a possible explanation for the results exposing rats to diets with equal amounts of carbohydrates using the same paradigm. • Test other antidepressants for this effect – SSRI’s as well as other classes of antidepressants. • Investigate the effects of a longer term exposure to low and high fat diets. • Test female rats in similar paradigms.

Hanging Wire test . To rule out differences in muscle strength that may have affected swim behavior, the rats were tested in the Hanging Wire Test. Briefly, rats were placed on top a metal wire cage top where they gripped the wire top. Once the rat gripped the wire cage top the cage lid was flipped over the causing the rat to hang from the cage top. The amount of grip time was measures in seconds.

References

Ferrari AJ. et al. (2013) Burden of Depressive Disorders by Country, Sex,Age, and Year: Findings from the Global Burden of Disease Study. 2010. PLoS Med, 10(11): e1001547. Hu, S., et al. (2018). Dietary Fat, But Not Protein or Carbohydrate, Regulates Energy Intake and CausesAdiposity in Mice. Cell Metabolism. doi.org/10.1016/j.cmet.2018.06.010 SubstanceAbuse and Mental Health ServicesAdministration, Results from the 2013 National Survey on Drug Use and Health: Mental Health Findings, NSDUH Series H-49, HHS Publication No. (SMA) 14-4887. Rockville, MD: SubstanceAbuse and Mental Health Services Administration, 2014 . Sumaya, IC., Bailey, D., & Catlett, S. Differential effects of a short-term high-fat diet in an animal model of depression in rats treated with the 5-HT 3 receptor antagonist, ondansetron, the 5-HT 3 receptor agonist, 2-Methyl-5-HT, and the SSRI, fluoxetine. Pharmacology, Biochemistry, and Behavior. Volume 144, Mar 2016.

A 2X2 between subjects ANOVA showed a significant main effect for Drug, F (1,31) = 11.72 , p = .002. There was also a trend for a main effect for Diet, F (1,31) = 4.05 , p = .053.

Previous Research from our Lab

Procedure. After a seven-day acclimation period rats were individually housed and randomly assigned into two groups: low-fat (n = 18) and a high fat group (n = 18). All rats were fed their respective diets adlibitum for seven days and weight was measured daily. On the eighth day the rats were further randomized into two different drug treatment conditions, vehicle (distilled water) and fluoxetine (10mg/kg, IP). The rats were injected one hour prior to testing in the Forced Swim Test. After performing the swim test, each rat was dried off and placed back into its home cage and monitored until it was completely dry. Testing occurred over a two-day period between the hours of 1000 hours and 1200 hours.

This research was supported by the Student Research Scholars Program at CSUB ,The Gayle and Ben Batey Neuroscience Fund and the CSUB MARC U*Star Program, NIH Grant (5T34GM118212-03.

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