Physical training reverses defect in 3-ketoacid CoA-transferase activity in skeletal muscle of diabetic rats

Abstract

. Physical training reverses defect in 3-ketoacid CoAtransferase activity in skeletal muscle of diabetic rats. Am J Physiol Endocrinol Metab 288: E748 -E752, 2005; doi:10.1152/ajpendo.00515. 2004.-To investigate one potential mechanism whereby physical training improves the plasma concentration of ketone bodies in experimental diabetes mellitus, we measured the activity of 3-ketoacid CoA-transferase, the key enzyme in the peripheral utilization of ketone bodies. Diabetes was induced with streptozotocin (50 mg/kg) and training carried out on a treadmill with a progressive 10-wk program. Diabetes resulted in an increase (P Ͻ 0.001) in plasma concentration of ␤-hydroxybutyric acid in sedentary rats, which was partly reversed by training (P Ͻ 0.001). Diabetes was also associated with a decreased activity of 3-ketoacid CoA-transferase in gastrocnemius muscle. When expressed per total gastrocnemius, training increased the activity of 3-ketoacid CoA-transferase by 66% in nondiabetic rats (P Ͻ 0.001) and by 150% in diabetic rats (P Ͻ 0.001), the decrease present in diabetic rats being fully reversed by training. Simple linear regression between the log of 3-ketoacid CoA-transferase activity and the log of plasma ␤-hydroxybutyric acid levels showed a statistically significant (r ϭ 0.563, P Ͻ 0.001) negative correlation. The beneficial effects of training on plasma ketone bodies in diabetic rats are probably explained, at least in part, by an increase in ketone body utilization, mediated by an increase in skeletal muscle 3-ketoacid CoA-transferase activity.

A high-MUFA diet alone does not affect ketone body metabolism, but reduces glycated hemoglobin when combined with exercise training in diabetic rats

“…The results showed that diabetic rats in the EX group did not exhibit any improvement in glucose metabolism, while their sedentary counterparts had an average glucose level of more than 400 mg/dL at the end of the 12-week experiment. This finding is consistent with previous investigations, which indicated that exercise training improved glucose homeostasis in rats with mild STZinduced diabetes [34][35][36], but not in those with a severe diabetic state [6,9,37,38]. In this study, MUFA diet tended to reduce fasting plasma glucose levels, but no additional reduction was seen in combination with exercise.…”

“…Moreover, exercise training also exhibited an inhibitory effect on hepatic ketone synthesis and a stimulatory effect on muscle ketone use. These observations confirm the previous reports in diabetic rat model that exercise training can lower ketone body concentration through a combination of lower NEFA levels, decreased hepatic ketone synthesis [10], and enhanced muscle ketone utilization pathway [9]. However, ketone body use referred to here is ketone body oxidation, i.e.…”

“…The exercise training protocol used in the present study was modified from that used by El Midaoui et al [9]. A progressive training program involved a moderate-intensity exercise performed on a motorized treadmill (SportsArt 1190; Woodinville, WA, USA) with 8% slope twice daily (between 10:00 AM and 12:00 PM, and between 17:00 PM and 19:00 PM), 5 days/week for twelve weeks.…”

“…Furthermore, exercise training is reported to reduce plasma FFA and β-hydroxybutyric acid levels in a rat model of diabetes induced by streptozotocin (STZ) [8][9][10], through a reversal of defective activity of 3-ketoacyl-CoA transferase in muscle ketone use [9], and a decrease in the overall activity of ketone synthesis pathway in the liver [10].…”

Interpreting the overall metabolic consequences of exercise in diabetes

“…To the Editor: I read with great interest the important and carefully designed study by El Midaoui et al (1). This study is the first to have prudently evaluated the effects of regular exercise on 3-ketoacid CoA-transferase activity in gastrocnemius muscle in the streptozotocin model of diabetes.…”