Ghrelin is a gastric
hormone increased during
caloric restriction and fat depletion. A role of
ghrelin in the regulation of
lipid and energy metabolism is suggested by fat gain independent of changes in food intake during exogenous
ghrelin administration in rodents. We investigated the potential effects of peripheral
ghrelin administration (two times daily 200-micrograms [DOSAGE ERROR CORRECTED] sc injection for 4 days) on
triglyceride content and mitochondrial and lipid metabolism gene expression in rat liver and muscles. Compared with vehicle,
ghrelin increased
body weight but not food intake and circulating
insulin. In liver,
ghrelin induced a lipogenic and glucogenic pattern of gene expression and increased
triglyceride content while reducing activated (phosphorylated) stimulator of
fatty acid oxidation,
AMP-activated protein kinase (AMPK, all P < 0.05), with unchanged mitochondrial oxidative
enzyme activities. In contrast,
triglyceride content was reduced (P < 0.05) after
ghrelin administration in mixed (gastrocnemius) and unchanged in oxidative (soleus) muscle. In mixed muscle,
ghrelin increased (P < 0.05) mitochondrial oxidative
enzyme activities independent of changes in expression of fat metabolism genes and phosphorylated AMPK. Expression of
peroxisome proliferator-activated receptor-gamma, the activation of which reduces muscle fat content, was selectively increased in mixed muscle where it paralleled changes in oxidative capacities (P < 0.05). Thus
ghrelin induces tissue-specific changes in mitochondrial and lipid metabolism gene expression and favors
triglyceride deposition in liver over skeletal muscle. These novel effects of
ghrelin in the regulation of lean tissue fat distribution and metabolism could contribute to metabolic adaptation to
caloric restriction and loss of body fat.