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Influence of Weight Loss on Skeletal Muscle Mitochondrial Function and Metabolism in the Mature Horse
Obesity causes a multitude of metabolic issues in horses, yet stepwise alterations in glucose and lipid metabolic capability, mitochondrial capacity and oxidant status during weight loss have not been evaluated. We hypothesized that horses would display improvements in morphometric measurements, circulating metabolic markers, minimal model estimates of glucose tolerance and insulin sensitivity during weight loss over 96 d from an obese (7 to 8) to moderate (5) body condition score (BCS). Further, skeletal muscle contains subsarcolemmal (SSM) and interfibrillar (IFM) mitochondria, which respond differently to physiological stimuli; therefore, we hypothesized horses would display improvements in mitochondrial subpopulation function and reductions in circulating oxidant status markers during weight loss sampled every other week. Horses displayed significant decreases in all morphometric measurements (p ≤ 0.04) except for abdominal circumference (p = 0.08). A decrease in rump fat thickness from 11.5 ±1.2 to 6.1 ± 1.1 mm reflected decreasing body fat mass (p < 0.0001). Weight loss had no effect on circulating concentrations of glucose or insulin measured every other week. Insulin sensitivity increased from 1.08 ± 0.27 to 4.32 ± 1.59 x10-4 L*mU-1*min-1 with both reduction in BCS and weight loss (p ≤ 0.04). The disposition index, an assessment of β-cell function, tended to increase with percent weight loss (p=0.09) but not lower BCS. Plasma nitrate trended to decrease in response to BCS reduction and percent weight loss (p ≤ 0.06), whereas erythrocyte total glutathione (p = 0.06) concentration increased with decreasing BCS. Mitochondrial electron transport chain complexes I and IV displayed greater activity in SSM than IFM (p ≤ 0.03), while all complexes in IFM had decreased activity due to both weight parameters (p ≤ 0.01). Interactions between subpopulation complex IV activity and weight loss markers (p < 0.05) were displayed. Citrate synthase activity, indicating mitochondrial number, was greater in SSM than IFM (p < 0.0001) but was unaffected with weight loss. Lipid peroxidation was decreased with BCS change (p = 0.01) and weight loss (p = 0.02), displaying greater amounts in SSM than IFM (p≤0.02). Few changes in circulating markers along with minute alterations in minimal model parameters suggest that while horses were obese, metabolic function was conserved. Complex activitiy and lipid peroxidation alterations suggest IFM are more affected by weight loss, with large contributions from complex IV byproducts. Mitochondrial component flexibility may contribute individually to disease development along with athletic performance in the horse.
Keywords: Obesity, Mitochondria, Muscle