Interactions between myoglobin and fatty acid metabolism in heart and skeletal muscle.

摘要

Fatty acid metabolism is a critical energy source for highly oxidative muscle tissue such as is found in heart and other skeletal muscle. The metabolism of fatty acid involves many different processes including beta oxidation, Krebs cycle, and the electron transport chain. There are many factors affecting the rate of fatty acid metabolism including substrate availability, relative enzyme activity, and allosteric regulation.;Myoglobin is a heme protein found exclusively in heart and oxidative skeletal muscle. The traditional role for myoglobin is acting as an oxygen reservoir as well as a facilitator of oxygen diffusion in oxidative muscle tissue. A study using H1 NMR has shown a specific interaction of myoglobin with fatty acid in solution. These results indicate a possible role for myoglobin in fatty acid metabolism in vivo.;To examine this interaction myoglobin knockout mice and FVB wild type mice were studied under control, fasted and trained conditions. The fasting protocol consisted of 24 hours with ad libitum access to water only. The training protocol consisted of 5 weeks of voluntary wheel running which has been shown in other studies to cause increases in muscle myoglobin concentration as well as increases in other measures of oxidative capability. The myoglobin knockout mice and FVB wild type mice demonstrated no difference between the groups in average distance run for each week. Both groups showed a statistically significant increase in distance from week 1 to week 2, beyond which showed no further increase through week 5.;The quantitative measurements of triglyceride in heart and skeletal muscle were made using enzymatic assays and spectrophotometer measurements. Heart and skeletal muscle samples were ground with sodium sulfate and extracted with a 2:1 chloroform: methanol solution. Extracted samples were evaporated and reconstituted in isopropanol for enzymatic assay. There was a statistically significant difference in triglyceride concentration between myoglobin knockout mice and FVB wild type mice in muscle and heart.;The fasting protocol showed a statistically significant increase in triglyceride concentration in both myoglobin knockout mice and FVB wild type heart and muscle. Furthermore, there was a statistically significant decrease in the concentration of triglyceride in trained wild type and trained myoglobin knockout heart and muscle. Plasma triglyceride was measured with the same enzymatic assays to measure the blood lipid levels which can have a significant effect on muscle triglyceride.;Plasma triglyceride showed no difference between myoglobin knockout mice and FVB wild type mice. There was a statistically significant increase in plasma triglyceride among the trained group of mice indicating an increase in the available fatty acid in the circulation. Myoglobin determination was performed through optical spectrophotometry to measure changes in myoglobin concentration with training. There was a statistically significant increase in the myoglobin in skeletal muscle with training but not in the cardiac muscle.;Although myoglobin knockout mice retain their exercise capacity, their fatty acid metabolism is affected causing a decrease in triglyceride storage under a variety of metabolic conditions. This may be related myoglobin affecting the solubility of fatty acid in the cytoplasm.