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Acylation state determines the action of ghrelin on energy and glucose metabolism

Heppner, Kristy M.
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1380556886

Abstract Details

2013, PhD, University of Cincinnati, Medicine: Neuroscience/Medical Science Scholars Interdisciplinary.
Ghrelin is a gastrointestinal hormone that activates the ghrelin receptor (GHSR) in hypothalamic neurons to promote feeding and peripheral lipid storage. Ghrelin contains a unique acyl modification that is esterified to the peptide molecule. The recent discovery of the ghrelin acylating enzyme, ghrelin O-acyltransferase (GOAT), has provided a deeper understanding of the acylation process and actions of acyl ghrelin (AG) versus des-acyl ghrelin (dAG). Our group previously demonstrated that GOAT utilizes various dietary fatty acids (FAs) as a substrate for ghrelin acylation. In the current study, we use both in vitro and in vivo approaches to demonstrate that ghrelin action on GHSR activation, food intake, body weight and fat mass can be modified by altering the FA side-chain length of the ghrelin peptide molecule. Additionally, we find that AG and dAG act in the central nervous system to increase glucose-stimulated plasma insulin levels indicating that this function of ghrelin is independent of its acylation state. Finally, we combine genetic and pharmacological approaches to demonstrate that the regulation of glucose tolerance by GOAT action is dependent on calorie restriction and age. Collectively, these data systematically dissect the function of ghrelin acylation in regulating energy and glucose metabolism.
Stephen Benoit, Ph.D. (Committee Chair)
Jenny Tong, MD MPH (Committee Member)
Darleen Sandoval, Ph.D. (Committee Member)
Randy Seeley, Ph.D. (Committee Member)
Matthias Tschoep, M.D. (Committee Member)
142 p.
Neurology
ghrelin; ghrelin O-acyltransferase; growth hormone secretagogue receptor; metabolism; fatty acid; obesity

Recommended Citations

Citations

  • Heppner, K. M. (2013). Acylation state determines the action of ghrelin on energy and glucose metabolism [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1380556886

    APA Style (7th edition)

  • Heppner, Kristy. Acylation state determines the action of ghrelin on energy and glucose metabolism. 2013. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1380556886.

    MLA Style (8th edition)

  • Heppner, Kristy. "Acylation state determines the action of ghrelin on energy and glucose metabolism." Doctoral dissertation, University of Cincinnati, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1380556886

    Chicago Manual of Style (17th edition)

ucin1380556886
451
© 2013, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.