Long-lasting and widespread effects of fructose on behavior, metabolism, and cytokine gene expression: Insight from in vivo and in vitro studies Público

Abstract

A rise in fructose consumption has paralleled a similar rise in metabolic dysfunction, particularly in Western countries. Fructose, a large component of added sugars in processed foods and beverages, is not only differentially metabolized by the body compared to glucose, but has also been linked to increases in metabolic disorders, impaired HPA axis activity, and inflammation. Adolescents, some of the top consumers of diets high in fructose, may be more susceptible to the detrimental effects of fructose enriched foods and other environmental factors such as chronic stress. In the presented studies, I first evaluated the effects of a high fructose diet and chronic stress on behavior and HPA axis in adolescent male rats. In behavioral testing during adulthood, only fructose-fed animals demonstrated an increase in depressive-like and anxiety-like behaviors, as well as HPA axis hyperactivity. Notably, these animals were not more vulnerable to the consequences of chronic stress. In the second experiment, I further hypothesized that fructose-fed animals would demonstrate altered metabolic states. Our data indicated that a high-fructose diet fed during adolescence does in fact alter weight, food consumption, blood glucose, and visceral adiposity. In order to determine whether fructose was directly having an effect on neuronal and glial cell survival and gene expression, I used an in vitro model. I found that fructose exposure in neurons and co-cultures of neurons and microglia was detrimental to cell viability. Next, I evaluated inflammation as a potential mechanism for the changes observed in vivo and in vitro. Surprisingly, my data suggested that proinflammatory gene expression is decreased in neurons and co-cultured neurons and microglia. I propose that the cytokines TNF-α and IL-6 are downregulated in co-cultures due to the protective roles of these cytokines and cross-talk between neurons and microglia. These studies not only demonstrate the damaging effects of a high fructose diet given to adolescent rats, but they correspondingly illustrate the negative effects of fructose on cultured neurons and microglia.

Table of Contents

INTRODUCTION. 1

METHODS. 18

RESULTS. 26

DISCUSSION. 31

REFERENCES. 42

FIGURES. 49

Figure 1. 49

Figure 2. 50

Figure 3. 51

Figure 4. 52

Figure 5. 53

Figure 6. 54

Figure 7. 55

Figure 8. 56

Figure 9. 57

Figure 10. 58

About this Honors Thesis

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School	Emory College
Department	Neuroscience and Behavioral Biology
Degree	BS
Submission	Honors Thesis
Language	English
Research Field	Biology, Physiology Biology, Neuroscience
Palabra Clave	Fructose inflammation Adolescence metabolic dysfunction depressive-like and anxiety-like behaviors IL-6, TNF-alpha
Committee Chair / Thesis Advisor	Neigh, Gretchen, Emory University
Committee Members	Sanchez, Mar, Emory University Maney, Donna, Emory University

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