Modulation of bio-behaviors and diabesity by dietary factors

Kaczmarczyk, Melissa

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https://hdl.handle.net/2142/31960 Copy

Description

Title

Modulation of bio-behaviors and diabesity by dietary factors

Author(s)

Kaczmarczyk, Melissa

Issue Date

2012-06-27T21:21:33Z

Director of Research (if dissertation) or Advisor (if thesis)

Freund, Gregory G.

Doctoral Committee Chair(s)

Fahey, George C.

Committee Member(s)

• Freund, Gregory G.
• Miller, Michael J.
• Dilger, Ryan N.

Department of Study

Nutrition Sciences

Discipline

Nutrition Sciences

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• obesity
• nutrition
• cognition
• fiber
• diabetes
• pectin
• Attention deficit hyperactivity disorder (ADHD)

Abstract

Obesity is associated with a host of co-morbidities including hyperglycemia, insulin resistance, Type II diabetes (T2D), and cognitive deficit. The present study examined the modulation of weight, blood metabolites, bio-behaviors, and neuro-immune function by a high fat diet. C57BL/6J male mice were fed a 60% fat diet (high fat diet; HFD) or a 10% fat (low fat diet; LFD) for 1 or 3 weeks post-weaning, after which mice were subjected to behavioral testing. HFD-fed mice had increased anxietal-like and reward seeking behavior and decreased performance in spatial and non-spatial memory tasks compared to mice fed a LFD. There was no difference in spontaneous locomotion or depressive-like behavior between diet groups. Additionally, non-spatial memory deficit was restored in mice fed HFD for 1 week by feeding a LFD for 1 week. Interestingly, IL-1R1 -/- mice displayed non-spatial memory deficit regardless of diet, implicating a role for IL-1 in HFD- induced memory deficit. Analysis of the mRNA expression of key cytokines and growth factors in the hippocampus, hypothalamus, and cortex did not show differences in the expression of IL-1 or IL-1 receptors after 1 week of diet feeding, but showed reduced expression of two key growth factors related to memory, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), in HFD-fed mice compared to LFD-fed mice. Finally, memory impairment in HFD-fed mice was corrected with administration of methylphendidate, a stimulant that increases the synaptic concentration of dopamine and norepinephrine by blocking dopamine transporters. Anti-depressants, desipramine and reboxetine, both norepinephrine re-uptake inhibitors, did not correct memory deficit in HFD-fed mice. Dietary fiber (DF) is associated with a reduction in the risk of obesity and T2D. The present study also examined the protective effect of soluble and insoluble fibers on weight gain and T2D. C57BL/6J male mice were fed a HFD or LFD supplemented with pectin, cellulose, resistant starch, or fructooligosaccharide for 10-12 weeks. Mice fed a HFD + 10% pectin were protected against weight gain, while mice fed a HFD + 5% pectin, 5% pectin and 5% cellulose, 10% resistant starch, or 10% fructooligosaccharides were not. Supplementation of a HFD with 10% pectin also slowed HFD-induced elevation of fasting blood glucose and significantly decreased blood glucose concentrations when presented with an intraperitoneal glucose challenge. Supplementation of a HFD with 10% pectin slowed weight gain in IL1R1-/-, IL4-/-, and MyD88-/- mice, but not in TLR4-/- or TLR2-/- mice. Finally, fecal lipid excretion was significantly increased in pectin-supplemented animals compared to cellulose, suggesting that pectin’s ability to form viscous gels results in decreased lipid digestion and absorption, contributing to the differences noted in weight gain between diet groups. This research demonstrates that HFD-feeding has an immediate, detrimental effect on bio-behaviors in juvenile mice. In addition, this research demonstrates that HFD-induced weight gain and hyperglycemia may be delayed by pectin supplementation.

Graduation Semester

2012-05

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http://hdl.handle.net/2142/31960

Copyright and License Information

Copyright 2012 Melissa Kaczmarczyk

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