Document Type

Open Access Thesis

Embargo Period

9-14-2015

Degree Program

Kinesiology

Degree Type

Master of Science (M.S.)

Year Degree Awarded

2015

Month Degree Awarded

September

Advisor Name

Sarah

Advisor Last Name

Witkowski

Co-advisor Name

Edward

Co-advisor Last Name

Debold

Third Advisor Name

Lisa

Third Advisor Last Name

Minter

Abstract

ABSTRACT

Introduction: Cardiometabolic syndrome is considered a chronic low-grade inflammatory condition that affects various organs and tissues. Individuals with type 2 diabetes mellitus (T2DM) and obesity are at an increased risk for developing the cardiometabolic syndrome and have greater rates of cardiovascular disease (CVD). These conditions are also associated with increased systemic and local inflammation and greater expression of pro-inflammatory markers such as monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor-α (TNF-α), and interleukin 1β (IL-1β) in many tissues. The heart is adversely affected by the inflammation and metabolic changes induced by diabetes and obesity. Nuclear transcription factor kappa B (NF-κB) activity is known to be related to inflammation and cytokine production. However, there is limited information on whether NF-κB signaling and inflammation play a role in early cardiac pathogenesis related to obesity and diabetes and whether lifestyle changes known to prevent or treat these diseases are effective in the heart. Purpose: Therefore, the purpose of this study was to compare the effect of exercise (EX) and caloric restriction (CR) to alter NF-κB signaling, inflammation, and markers of cardiac dysfunction in the heart of 20-week old Otsuka Long Evans Tokushima (OLETF) rats. Methods: Hearts of male 20 week old OLETF rats from a previous study (Crissey et al., 2014) were collected for gene expression (RT-PCR), NF-κB activity, and markers of inflammation and immune cell infiltration. Results: There were no significant differences detected in markers of cardiac dysfunction including, α-MHC, β-MHC, ANP, BNP, COL1, COL3 (all p>0.05). Second, 1-way ANOVA showed that there was trend for an overall effect of group (p=0.07) on

NF-κB activation where CR tended to be greater compared to SED and WR (p=0.06). Finally, there were no significant differences between groups in inflammatory and immune cell markers; CD4, F4/80, CD68, IL-1β, MCP-1, TGFB1, and TNF-α (all p>0.05). Conclusion: This study shows that at 20 weeks, a time when OLETF animals exhibit characteristics of the metabolic syndrome such as hypertension, mild obesity, and increased insulin resistance, EX and CR do not reduce markers of cardiac dysfunction and inflammation, potentially because inflammation does not influence the heart at this early time period in the development of the disease. Further, the trend of greater NF-κB activity in CR compared to EX and SED, needs further exploration.

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