Semester

Fall

Date of Graduation

2013

Document Type

Dissertation

Degree Type

PhD

College

Davis College of Agriculture, Natural Resources and Design

Department

Animal and Nutritional Sciences

Committee Chair

Kimberly M. Barnes

Committee Co-Chair

Stephen E. Alway

Committee Member

John M. Hollander

Committee Member

Holly S. Spooner

Committee Member

Janet C. Tou

Abstract

Obesity causes a multitude of metabolic issues in the horse, yet stepwise alterations in glucose and lipid metabolism, mitochondrial capacity and oxidant status during weight loss have yet to be analyzed. Skeletal muscle contains subsarcolemmal (SSM) and interfibrillar (IFM) mitochondria, which respond differently to physiological stimuli, impacting tissue and whole body oxidant status. We hypothesized that 8 light-type horses would display improvements in skeletal muscle mitochondrial subpopulation function and decreases in circulating oxidant status markers during weight loss from an obese (7 to 8) to moderate (5) body condition score (BCS). Additionally, we hypothesized improvements in morphometric measurements, circulating metabolic markers, along with glucose tolerance and insulin sensitivity would also be seen. Change in BCS and percent weight loss were related to decreases in all morphometric measurements (p<0.05) except for abdominal circumference (p<0.10). Measurements of body composition also decreased with regard to both weight loss parameters (p≤0.001). Circulating markers of lipid metabolism evaluated from non-fasting samples revealed no changes in non-esterified fatty acid (NEFA) or triacylglyceride concentration, yet ex vivo lipolysis media was decreased in response to weight loss (p=0.07) and BCS change (p=0.01). Insulin sensitivity calculated from baseline and post-weight loss intravenous glucose tolerance tests was improved after weight loss and corresponding BCS decline (p≤0.05) while the disposition index, reflecting beta-cell responsiveness, also increased due to weight loss (p=0.09). Plasma nitrate decreased in response to BCS reduction (p=0.06) and percent weight loss (p=0.06), whereas erythrocyte total glutathione (p=0.06) concentration increased with decreasing BCS, signifying improvements in oxidant status. Mitochondrial electron transport chain complex I and IV displayed greater activity in SSM than IFM (p≤0.05), while I, III, and IV in SSM had decreased activity due to BCS change and percent weight loss (p≤0.01). Interactions between SSM and IFM complex IV activity and both weight loss markers (p<0.05) were displayed. Citrate synthase activity, indicating mitochondrial number, was greater in SSM than IFM (p<0.0001) but remained unchanged with weight loss parameters. Lipid peroxidation was decreased due to BCS change (p=0.01) and weight loss (p=0.02), with greater concentration in SSM, but a larger decrease in IFM (p≤0.05). Alterations in complex activities and lipid peroxidation suggest IFM are more affected by weight loss, with large contributions from complex IV byproducts. Mitochondrial component flexibility may contribute individually to development and disease propagation along with athletic performance of the equine athlete. Lack of changes in circulating markers along with minimal changes in minimal model parameters suggest that while horses were obese, metabolic function was conserved. Further evaluation of metabolically healthy but obese horses may provide insight as to management and treatment of obesity associated maladies.

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