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Delayed Short-Term Secretory Regulation of Ghrelin in Obese Animals: Evidenced by a Specific RIA for the Active Form of Ghrelin

Department of Medicine and Clinical Science (H.A., H.I., E.K., K.M., Y.O., K.H., K.N.), Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan; Translational Research Center (K.T., T.A., K.K.), Kyoto University Hospital, Kyoto 606-8507, Japan; Division of Molecular Genetics, Institute of Life Science (M.K.), Kurume University, Kurume, Fukuoka 839-0861, Japan; and Department of Biochemistry (H.H., K.K.), National Cardiovascular Center Research Institute, Osaka 565-8565, Japan

Address all correspondence and requests for reprints to: Kazuhiko Takaya, M.D., Ph.D., Translational Research Center, Kyoto University Hospital, Kyoto 606-8507, Japan. E-mail: ktakaya{at}kuhp.kyoto-u.ac.jp.

Ghrelin is an acylated peptide, whose lipid modification is essential for its biological activities. Previous studies demonstrated that it strongly stimulates GH release and has a potent orexigenic action. Meanwhile, there is enough evidence showing that feeding states influence plasma ghrelin levels. Fasting stimulates ghrelin secretion, and feeding reduces plasma ghrelin levels. In this study we examined the regulation of plasma ghrelin by fasting in genetically obese animals considering its molecular forms. Plasma levels of active form of ghrelin as well as those of total ghrelin were reduced in ob/ob and db/db mice compared with those in their control mice. Zucker fatty (fa/fa) rats also showed lower plasma ghrelin levels by fasting than the control rats. Insulin-induced hypoglycemia, however, stimulated ghrelin secretion in the fasted fatty rats. Moreover, glucose injection was revealed to reduce plasma ghrelin levels in rats. The effect of the severity of obesity on secretory regulation of ghrelin was also studied. Older fatty rats showed low plasma ghrelin levels even after 48-h fasting. These data suggest that the short-term secretory regulation of total ghrelin and the active form of ghrelin is delayed in obese animals and that blood glucose levels may be involved in the delayed regulation.

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