FP30-2 Ghrelin Release is Altered in Primary Gastric Mucosal Cell Cultures from Diet-Induced Obese Mice

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP30-Central Regulation of Appetite & Feeding
Basic
Monday, June 17, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 10:50 AM
Room 304 (Moscone Center)

Poster Board MON-680
Aki Uchida*, Won-Mee Park and Jeffrey Marc Zigman
UT Southwestern Medical Center, Dallas, TX
Ghrelin is a peptide hormone produced in a distinct gastric enteroendocrine cell type.  Plasma ghrelin levels are dynamic and fluctuate with metabolic status – rising before a meal and declining after a meal.  In humans and rodents, ghrelin levels are inversely correlated with bodyweight, with lower circulating ghrelin levels in obese as compared to lean individuals.  In addition, the fluctuation of ghrelin levels observed in lean individuals before and after a meal are either not observed or severely blunted in obese individuals.  The reduction in circulating ghrelin levels in obese individuals seem to reflect a physiological adjustment to prolonged positive energy balance, although the exact mechanisms mediating this phenomenon are not known.  The goal of this study was to determine the mechanism(s) regulating the altered ghrelin levels in obesity.  In particular, we set out to test the hypothesis that the obesity-related decrease in plasma ghrelin results from altered responsiveness of ghrelin cells to known mediators of ghrelin secretion, including norepinephrine (a secretagogue) and D-glucose (an inhibitor).  C57Bl6/J mice were fed a high-fat diet or standard rodent chow for 15 weeks starting at 4 weeks of age.  The high fat diet-fed mice developed diet-induced obesity (DIO), with increased bodyweight and fasting glucose levels and decreased fasting ghrelin levels compared to the standard rodent chow-fed lean controls.  Using a primary gastric mucosal culture generated from DIO and lean mice, we measured the secretion of ghrelin in response to norepinephrine and glucose treatments.  We found that cultures generated from DIO mice had diminished sensitivity to norepinephrine and glucose levels in the media.  These results suggest that the reduced plasma ghrelin levels and altered ghrelin fluctuations associated with obesity occur at least in part due to decreased responsiveness of the ghrelin cells to two key physiological cues, norepinephrine and glucose.

Nothing to Disclose: AU, WMP, JMZ

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

Sources of Research Support: NIH 2T32DK007307-32A1 (to AU); International Research alliance with The Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen (to JMZ)