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Alterations of Plasma Ghrelin Levels in Rats with Lipopolysaccharide-Induced Wasting Syndrome and Effects of Ghrelin Treatment on the Syndrome

Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine (Y.H., N.K., K.M., K.N.), Kyoto 606-8507, Japan; Translational Research Center (T.A., H.H., K.K.), Kyoto University Hospital, Kyoto 606-8507, Japan; and Department of Biochemistry, National Cardiovascular Center Research Institute (H.H., K.K.), Osaka 565-8565, Japan

Address all correspondence and requests for reprints to: Dr. Takashi Akamizu, Translational Research Center, Kyoto University Hospital, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan. E-mail: akataka{at}kuhp.kyoto-u.ac.jp.

Ghrelin not only strongly stimulates GH secretion, but is also involved in energy homeostasis by stimulating food intake and promoting adiposity through a GH-independent mechanism. These effects of ghrelin may play an important role in the pathophysiology of inflammatory wasting syndrome, in which both the somatotropic axis and energy balance are altered. In this study we investigated plasma ghrelin concentrations after lipopolysaccharide (LPS) administration to rats, a model of the wasting syndrome and critical illness. In addition, the therapeutic potential of the antiwasting effects of ghrelin was explored using LPS-injected rats. A single LPS injection suppressed plasma ghrelin levels 6 and 12 h later. Maximal reduction was observed 12 h after LPS injection, in a dose-dependent manner. In contrast, plasma ghrelin levels were elevated after repeated LPS injections on d 2 and 5. Peripheral administration of ghrelin twice daily (10 nmol/rat) for 5 d increased body weight gain in repeated LPS-injected rats. Furthermore, both adipose tissue weight and plasma leptin concentrations were increased after ghrelin administration in these rats. In conclusion, plasma ghrelin levels are altered in LPS-injected rats, and ghrelin treatment may provide a new therapeutic approach to the wasting syndrome and critical illness.

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