Influence of a long-term high-fat diet on ghrelin secretion and ghrelin-induced food intake in rats.

The aims of this study were: (1) to define the extent to which a high-fat (HF) diet given on a long-term basis reduces resting plasma ghrelin (total [acyl+des-acyl]) levels and the plasma ghrelin (total) response to fasting, (2) to determine whether a chronic HF diet modifies the orexigenic activity of acyl-ghrelin, (3) whether insulin pretreatment inhibits the plasma ghrelin (total) response to fasting, and (4) the extent to which pioglitazone (PIO) treatment will increase stomach and plasma ghrelin (total) levels in rats fed a HF diet. PIO is a drug given to diabetics which improves insulin resistance. Our findings show that a chronic HF diet given for either 10 or 60 weeks exerts a persistent inhibitory effect on resting plasma ghrelin (total) levels. Additionally, the plasma ghrelin (total) elevation to overnight fasting is not altered in rats fed a HF diet on a long-term basis. A HF diet does not impair the ingestive response to acyl-ghrelin. Together, these results suggest that acyl-ghrelin serves as an important orexigenic factor. Results show that insulin pretreatment does not inhibit the plasma ghrelin (total) response to fasting suggesting that meal-induced insulin secretion does not have a role in reducing ghrelin (total) secretion. In rats fed a HF diet, PIO administration increases stomach ghrelin (total) levels. Because PIO can reduce systemic glucose and lipid levels, our findings suggest that elevated glucose and lipid levels are part of the inhibitory mechanism behind reduced ghrelin (total) secretion in rats fed a HF diet.