Long-term caloric restriction up-regulates PPAR gamma co-activator 1 alpha (PGC-1 ) expression in mice.

ABSTRACT

The peroxisome proliferator-activated receptor (PPAR) gamma co-activator 1 alpha (PGC-1 ), a signal-sensing transcriptional co-activator in association with many nuclear receptors regulates various genes that control energy balance in animals. In this study, the effect of long-term caloric restriction (CR) (alternate days of fasting for 3 months) on the expression of PGC-1 protein in various tissues was investigated in mice. Western blot analyses showed positive immunoreactive PGC-1 (~92 kDa) signal from various tissues. Heart, kidney and skeletal muscles expressed significant levels of PGC-1 , while a comparatively lower level was detected in the liver, small intestine and brain. The expression of PGC-1 was the highest and lowest in the heart and liver respectively. CR mice exhibited a significant increase in PGC-1a level in the heart (5.13-fold), kidney (3.57-fold), skeletal muscle (3.02-fold), liver (2.60-fold), small intestine (2.45-fold) and brain (2.05-fold), compared to normal (ad libitum) fed. The elevation in PGC-1 level, especially in highly oxidative tissues such as heart, kidney and skeletal muscle of CR mice might synergistically up-regulate genes that require PGC-1 co-activation. Taken together, the up-regulation of PGC-1 expression might potentially support optimal energy metabolism and biochemical adaptation, necessary for maintaining energy homeostasis during long-term CR.