Coping with reduced energy sources entails drastic morphological and functional changes in skeletal muscle, but the sequence of events required classification. We found that gastrocnemius muscle from food-deprived rats shows acute rises in peroxisome proliferator activated receptor (PPAR) gamma coactivator (PGC) -1alpha/PPAR delta nuclear protein and myosin heavy chain (MHC) Ib protein, while type I fibers accumulate and the muscle tissue appears redder. AMP levels, phosphorylation of both AMP-activated protein kinase (AMPK) and its downstream target acetyl coenzyme A carboxylase (ACC) are induced within 6 h. Rapidly increased MyoD mRNA levels are followed by an increase in uncoupling protein (UCP) 3 (UCP3) transcription. Increased serum fatty acid levels coincide with increases in mitochondrial UCP3 protein levels and fatty acid oxidation. Accompanying this is a decrease in AMPK phosphorylation, reversible upon nicotinic acid treatment, indicating that fatty acids may modulate this kinase's activity after the metabolic challenges posed by food deprivation.