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Am J Physiol Regul Integr Comp Physiol (March 12, 2008). doi:10.1152/ajpregu.00035.2008
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Submitted on January 17, 2008
Accepted on March 6, 2008

Peripheral Ghrelin Treatment Stabilizes Body Weights of Senescent Male Brown Norway Rats at Baseline and After Surgery

Michi Yukawa1, David S. Weigle2, Charles D. Davis3, Brett T. Marck4, and Tami H. Wolden-Hanson5*

1 Gerontology and Geriatric Medicine, University of Washington, Seattle, Washington, United States
2 Medicine, University of Washington, Seattle,, Washington, United States
3 GRECC, VA Puget Sound Health Care System, Seattle,, Washington, United States
4 Seattle, Washington, United States; GRECC, VA Puget Sound Health Care System, Seattle,, Washington, United States
5 GRECC, VA Puget Sound Health Care System, Seattle,, Washington, United States; Gerontology & Geriatric Medicine, University of Washington, S-182-GRECC, VA Puget Sound, Seattle, Washington, 98108, United States

* To whom correspondence should be addressed. E-mail: twh{at}u.washington.edu.

Unintentional weight loss may occur spontaneously in older humans and animals. Further weight losses after surgery or illness in the older patients result in increased morbidity, mortality, and hospital readmission rate. A growing body of work has shown increased appetite and weight gain in response to administration of ghrelin. We conducted two studies in senescent male Brown Norway rats to assess the ability of peripheral administration of ghrelin to increase body weight and food intake. One study assessed the effect of 2 weeks of daily subcutaneous ghrelin administration (1mg/kg/d) to senescent rats in a baseline condition; a second study used the same administration protocol in an interventional experiment with aged rats subjected to a surgery with 10-15% blood loss, as a model of elective surgery. In both studies, animals receiving ghrelin maintained their body weights, while control animals lost weight. Body weight stability was achieved in ghrelin-treated animals despite a lack of increase in daily or cumulative food intake in both experiments. Hormone and pro-inflammatory cytokine levels were measured before surgery and after 14 days of treatment. Ghrelin treatment appeared to blunt declining ghrelin levels and also to blunt cytokine increases seen in the surgical control group. The ability of peripheral ghrelin treatment to maintain body weights of senescent rats without concomitant increases in food intake may be due to its known ability to decrease sympathetic activity and metabolic rate, perhaps by limiting cytokine-driven inflammation.







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