The Inhibition of Gastric Ghrelin Production by Food Intake in Rats Is Dependent on the Type of Macronutrient

Ghrelin is a peptide mainly produced by the stomach that increases food intake and body weight. Ghrelin expression increases with fasting and is diminished by re-feeding, but although the expression of this hormone is regulated by the feeding state, the relation with diet composition is not yet well established. We have studied the inhibitory effect of the intake of two different macronutrients (fat and carbohydrates) on ghrelin production by the stomach in fasted rats, as well as the relation with another important signal in the regulation of energy balance, leptin. Ghrelin mRNA expression in the gastric mucosa was determined by Northern blotting, and leptin mRNA expression was determined by Northern blotting in the adipose tissue and by RT-PCR in the stomach; circulating and gastric concentrations of ghrelin and leptin were measured by enzyme immunosorbent assay and ELISA, respectively. Our results showed an increase in ghrelin mRNA levels in response to 14 h of fasting. Food intake for 20 min after the fast produced a decrease in ghrelin mRNA expression that was recovered in 45 min in rats that ate the fat diet, whereas levels remained low when rats ate the carbohydrate diet. Serum ghrelin followed a similar tendency. The decrease in ghrelin expression by feeding was associated with an increased expression of gastric leptin only when animals ate carbohydrates. We conclude that the inhibition of ghrelin production by the stomach after re-feeding of fasted rats is dependent on diet composition and can be related to the different satiating capacity of the ingested macronutrients, which is higher for carbohydrates than fat.