Date: June 7, 2007

Speaker's Name, Affiliation:

Matthias Tschoep
University of Cincinnati

Seminar Title:"Ghrelin"

Presiding Chair: Harry R. Kissileff, Ph.D.

Rapporteur: Kathleen L. Keller, Ph.D.

Attendees and their Affiliation:

Kathleen Keller	Columbia/Obesity Research Center
Harry Kissileff	Columbia/Obesity Research Center
Jennifer Nasser	New York Obesity Research Center
Marie- Pierre St.	Onge New York Obesity Research Center
Diane Klein	Columbia Psychiatry
Emmanuel Pothos	Tufts
Carol Maggio	New York Obesity Research Center
Joe Vasselli	New York Obesity Research Center
Barry Levin	VA Medical Center
Chris Ochner	New York Obesity Research Center
JA Grinker	U of Michigan
Gerard P. Smith	Cornell-Weill Medical Center
Christa Patterson	VA Medical Center
Judy Korner	Columbia University
Larry Nolan	Wagner College
Allan Harris	Manhattan Pharma
Karen Acroff	Brooklyn College
Kathleen Axen	Brooklyn College
Malki Miller	Brooklyn College
Virna Hallek	Brooklyn College
Allan Geliebter	New York Obesity Research Center
Steve Heymsfield	Merck
John Kral	SUNY Downstate
Hope Cassano	Columbia University

Summary:(Because data are not yet published, the speaker requested that this summary be brief)

Dr. Tschoep presented new data from his laboratory on the gut peptide "Ghrelin." Data from his laboratory suggest that the main effects of this hormone are in the brain, even though ghrelin is typically referred to as a "gut peptide." While initial studies suggested that ghrelin might be a hormone that initiates meals, it is now understood that ghrelin is involved in meal preparation-for metabolism of nutrients. Dr. Tschoep and colleagues have been studying the role of ghrelin with the use of knock-out animals. These animals are protected against obesity when on a high fat diet, but otherwise, they appear normal. When both the ghrelin gene and receptor are knocked out, animals tend to have slightly lower body weights and lower fat mass. Additional study of these animals will enrich the current knowledge of this gut peptide, and determine it's role in eating and body weight regulation.

Discussion:

Q. Were these knock-outs fully mature animals?
A. Yes, they were 1 year.

Q. You probably have a difference in amount of lean mass (between ghrelin knock-outs and wild)? Do you think this is the case?
A. Yes, we would expect that, but the difference is not significant.

Q. Did you try to re-feed animals with palatable foods? What would you expect then?
A. Not yet, but we will try this. Initial results weren't significant though.

Q. In the absence of ghrelin, are animals more sensitive to leptin administration?
A. We haven't tried leptin administration in these animals yet.

Q. What about growth hormones?
A. We haven't checked this yet, but we plan to look into IGFI. The assays aren't done yet.

Q. Do you have RMR in your animals?
A. [Didn't record response]

Q. How do you interpret the result that in obese humans, ghrelin tends to be lower?
A. I think it might be due to counter regulation in humans. There are so many other factors involved [with body weight regulation.]

Q. What happens if you re-administer ghrelin to these double knock outs (receptor and gene knock outs)?
A. We haven't tried that, mainly because we haven't had good luck in the past performing such experiments.

Q. Has the story about ghrelin receptors in the afferent vagus held up?
A. No. Wolfgang Langhans has done more rigorous studies and shown that this isn't the case.

Q. What about the receptor though, and its effects on glucose metabolism?
A. That could be correct, but I'm not sure.

Q. Do you get the same result when you knock out ghrelin in ob/ob mice?
A. You cannot knock out ghrelin in these animals, but as of yet, noone has tried to knock out the ghrelin receptor.

Q. What happens if you give ghrelin during administration of a high fat diet?
A. We haven't tried this yet.

Q. What about exercise? How is this effected in ghrelin knock-outs?
A. We have found that it decreases exercise, but others have found that it increases activity.

Q. Have you measured TAG in these animals?
A. Yes, and if anything, they are slightly increased.

Q. IS cholesterol lower in ghrelin KOs?
A. Yes, Also, if you knock out MC3 or MC4 receptors, cholesterol increases.

Q. When ghrelin is administered in animals and you see increases in food intake, is this administration at physiological levels?
A. It is higher.

Q. Do we have any idea what ghrelin concentration is at the critical receptor?
A. No, but we would need to know that to answer the question raised about physiological levels of ghrelin.

Q. What is the alternate splice form of ghrelin doing? Is it part of the ghrelin system?
A. I think so. It has a similar biological profile, but I'm curious as to why the expression pattern is so different.

Q. Do you see a therapeutic role for unacylated ghrelin?
A. We don't see anything in our studies, but other labs show some promising results.