Decreased Plasma Octanoylated Ghrelin Levels in Mice by Oleanolic Acid

• Published in: Journal of Oleo Science Vol. 68; no. 1; pp. 103 - 109
• Main Authors: Nakajima, Kensuke, Maeda, Narumi, Oiso, Shigeru, Kariyazono, Hiroko
• Format: Journal Article
• Language: English
• Published: Japan Japan Oil Chemists' Society 2019; Japan Science and Technology Agency
• Subjects: Acids; Acylation - drug effects; Administration, Oral; Animals; anti-obesity; Anti-Obesity Agents - therapeutic use; Body weight; C57BL/6J mouse; Caprylates - metabolism; Diet; Eating - drug effects; Fuel consumption; Gene expression; Ghrelin - blood; Male; Mice, Inbred C57BL; Octanoic acid; octanoylated ghrelin; oleanolic acid; Oleanolic Acid - administration & dosage; Oleanolic Acid - therapeutic use; Stomach; Substrates; Weight Gain - drug effects; octanoylated ghrelin; oleanolic acid; anti-obesity; C57BL/6J mouse
• ISSN: 1345-8957; 1347-3352
• DOI: 10.5650/jos.ess18148

Ghrelin is a stomach-derived peptide hormone with an appetite-stimulating effect. Octanoylation on the serine-3 residue of ghrelin by ghrelin O-acyl transferase (GOAT) is essential for its orexigenic effect. Mature octanoylated ghrelin is generated by the C-terminal cleavage of octanoylated proghrelin via prohormone convertases (furin, PC1/3, or PC2). We previously established an AGS-GHRL8 cell line that produces octanoylated ghrelin in the presence of octanoic acid, and found that oleanolic acid suppresses octanoylated ghrelin production in AGS-GHRL8 cells. Here, we investigated the effects of oleanolic acid in C57BL/6J mice fed a standard, high-fat, or high-glucose diet. Oral administration of oleanolic acid for seven days (20 or 40 mg/kg) reduced plasma octanoylated ghrelin levels and body weight gain in the standard diet-fed mice but not in other two diet-fed mice. There were no significant differences in ghrelin, GOAT, furin, PC1/3, and PC2 gene expression levels between the vehicle- and oleanolic acid-treated mice fed a standard diet. Octanoyl-CoA is a substrate for ghrelin octanoylation by GOAT. We found that oleanolic acid did not affect octanoyl-CoA production in vitro. Hence, the inhibitory effect of oleanolic acid on octanoylated ghrelin production may not be related to the decrease in octanoyl-CoA. The results of this study may provide valuable knowledge for the development of anti-obesity agents with an inhibitory effect on octanoylated ghrelin production.