FP08-5 Ghrelin Deletion Prevents Aging Associated Obesity and Muscle Dysfunction

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP08-Obesity: Novel Mechanisms of Body Weight Regulation
Basic/Translational
Saturday, June 15, 2013: 11:00 AM-11:30 AM
Presentation Start Time: 11:20 AM
Room 301 (Moscone Center)

Poster Board SAT-710
Jose Manuel Garcia*1, Bobby O Guillory2 and Tripti Halder3
1MEDVAMC/ Baylor Coll of Med, Houston, TX, 2Baylor College of Med, Houston, TX, 3MEDVAMC/ Baylor Coll MEd, Houston, TX
The prevalence of obesity increases dramatically with age and is associated with an increase risk of diabetes, cardiovascular disease, cancer and overall mortality. Aging is also associated with a decline in muscle function, leading to poor quality of life and increased mortality. Nevertheless, the mechanisms contributing to the development of obesity and muscle dysfunction in aged individuals have not been fully characterized. Ghrelin is an appetite-stimulating hormone and GH secretagogue that is known to decrease energy expenditure and to increase food intake, adiposity and body weight. The purpose of this study was to characterize the role of ghrelin during aging.

Body weight, body composition, food intake, locomotor activity, energy expenditure (EE), muscle strength and endurance were compared between young adult (6 month-old) and old (19 month old) ghrelin wild type (WT) and knock-out (KO) c57bl/6 male mice. Older animals had higher body weight and fat mass measured by NMR than younger animals in both genotypes. Although there was no difference in these parameters between young WT and KO animals, old KO animals had significantly lower body weight and fat mass than WT. Daily food intake and respiratory quotient (RQ) did not differ between groups. However, EE adjusted by LBM was significantly decreased by age in WT but not in KO animals. Spontaneous 24-h locomotor activity tended to decrease with aging in both genotypes although this difference did not reach significance. Treadmill performance and grip strength declined during aging and were improved with deletion of ghrelin.

In summary, in our model aging is associated with an increase in body weight and adiposity, and decreased EE, endurance and muscle strength. The increase in body weight and fat mass was ameliorated by deletion of the ghrelin gene only in aged animals. In spite of the known orexigenic effects of ghrelin at pharmacologic doses, the deletion of ghrelin did not cause changes in food intake. However, it prevented the decrease in EE seen with aging in WT animals. These data suggest that the differences in body weight and body composition induced by deletion of ghrelin in aged animals are due to differences in EE. Muscle performance was improved by deletion of ghrelin in spite of its known anabolic properties.

Disclosure: JMG: Principal Investigator, Aeterna Zentaris, Principal Investigator, Helsinn Therapeutics. Nothing to Disclose: BOG, TH

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Work funded by the Dept. of Veterans Affairs (MERIT BX000507 to JMG) and the NIH (AG040583 to JMG and T32AG000183 to BG).