Differential regulation of PGC-1alpha expression in rat liver and skeletal muscle in response to voluntary running.
BACKGROUND
The beneficial actions of exercise training on lipid, glucose and energy metabolism and insulin sensitivity appear to be in part mediated by PGC-1alpha. Previous studies have shown that spontaneously exercised rats show at rest enhanced responsiveness to exogenous insulin, lower plasma insulin levels and increased skeletal muscle insulin sensitivity. This study was initiated to examine the functional interaction between exercise-induced modulation of skeletal muscle and liver PGC-1alpha protein expression, whole body insulin sensitivity, and circulating FFA levels as a measure of whole body fatty acid (lipid) metabolism.


METHODS
Two groups of male Wistar rats (2 Mo of age, 188.82 +/- 2.77 g BW) were used in this study. One group consisted of control rats placed in standard laboratory cages. Exercising rats were housed individually in cages equipped with running wheels and allowed to run at their own pace for 5 weeks. At the end of exercise training, insulin sensitivity was evaluated by comparing steady-state plasma glucose (SSPG) concentrations at constant plasma insulin levels attained during the continuous infusion of glucose and insulin to each experimental group. Subsequently, soleus and plantaris muscle and liver samples were collected and quantified for PGC-1alpha protein expression by Western blotting. Collected blood samples were analyzed for glucose, insulin and FFA concentrations.


RESULTS
Rats housed in the exercise wheel cages demonstrated almost linear increases in running activity with advancing time reaching to maximum value around 4 weeks. On an average, the rats ran a mean (Mean +/- SE) of 4.102 +/- 0.747 km/day and consumed significantly more food as compared to sedentary controls (P < 0.001) in order to meet their increased caloric requirement. Mean plasma insulin (P < 0.001) and FFA (P < 0.006) concentrations were lower in the exercise-trained rats as compared to sedentary controls. Mean steady state plasma insulin (SSPI) and glucose (SSPG) concentrations were not significantly different in sedentary control rats as compared to exercise-trained animals. Plantaris PGC-1alpha protein expression increased significantly from a 1.11 +/- 0.12 in the sedentary rats to 1.74 +/- 0.09 in exercising rats (P < 0.001). However, exercise had no effect on PGC-1alpha protein content in either soleus muscle or liver tissue. These results indicate that exercise training selectively up regulates the PGC-1alpha protein expression in high-oxidative fast skeletal muscle type such as plantaris muscle.


CONCLUSIONS
These data suggest that PGC-1alpha most likely plays a restricted role in exercise-mediated improvements in insulin resistance (sensitivity) and lowering of circulating FFA levels.
Matiello
Renata
R
Laboratory of Medical Investigation, LIM-18, Division of Endocrinology and Metabolism, Hospital of Clinics, School of Medicine, University of Sao Paulo, Av Dr Arnaldo, 455, 3rd floor, room 3324, Sao Paulo, 01246-903, Brazil. salman.azhar@va.gov.
Fukui
Rosa T
RT
Silva
Maria Er
ME
Rocha
Dalva M
DM
Wajchenberg
Bernardo L
BL
Azhar
Salman
S
Santos
Rosa F
RF