Presiding Chair: Harry R. Kissileff, Ph.D.
Rapporteur: Kathleen L. Keller, Ph.D.
Date:February 16th, 2006
Title:"Nutrients, CCK, and Human GI Physiology"
Speaker:David G. Thompson
Attendees and their Affiliation:
| Kathleen Keller | Columbia/Obesity Research Center | |
| Harry Kissileff | Columbia/Obesity Research Center | |
| Anthony Azzara | AECOM | |
| Rhoda Guen | Columbia | |
| Jason Halford | Liverpool | |
| Andreas Nygaard Madson | AECOM | |
| Esther Van de Wall | AECOM | |
| Gerry Smith | Weill-Cornell | |
| Stephanie J. Kuca | Merck | |
| James Hubert | Merck | |
| Susi Lee | Merck | |
| Rebecca Gordon | SLR-ORC | |
| Laurence Nolan | Wagner College | |
| Joseph LeSaurer | Barnard College | |
| Joe Vasselli | St. Luke's Columbia | |
| Carol Maggio | St. Luke's Columbia | |
| Katherine Halmi | Cornell | |
| Emmanuel Pothos | Tufts Univ. School of Medicine | |
| Allan Geliebter | St. Luke's | |
| Doug Mook | Astoria |
Summary:(Provided by the Speaker)
The recognition of nutrients by the gut is fundamental to digestion and eating behaviour. This nutrient recognition is mediated by mucosal enteroendocrine cells which sample luminal composition and signal to the brain both by circulation and afferent vagal nerves. Cholecystokinin, the principle peptide signaling molecular in the upper gut, is released by lipids in the form of free fatty acids and a chain length of 12 or more. CCK limits meal intake in man in association with gastric emptying delay and gastric distension.
A number of important recent developments mean that it is now possible to understand CCK mediated pathways with greater precision in man. These include specific CCK-1 antagonists, brain imaging and simple non-invasive physiological measurements suitable for population studies. Using these new tools it has been possible to show i) how CNS centers are activated by nutrients; ii) the degree of variation in responses to nutrients in the population; iii) that vagal pathways are dynamic and responsive to state of nutrient intake.
Discussion:
Q. A recent study has found that lauric acid also has an effect on CCK release, similar to that of decanoic acid. Would you expect that?
A. Yes, you would. The chain lengths of these fatty acids are the same.
Q. Is that (CCK 1 receptor antagonist) a 1-A antagonist?
A. Yes
Q. For your brain imagine, what period of time did you observe subjects?
A. 10 minutes, followed by a meal, and then an additional 20 minutes of observation.
Q. Have you looked at a time course effect?
A. Yes. I'll show you that data in the next slide.
Q. Do you have satiety ratings for your subjects?
A. Yes. I will get to those soon.
Q. What are the red bars referring to on your graphs?
A. Those are confidence intervals.
Q. How many minutes does each interval represent?
A. 2 minutes each
Q. Why is there no change in CCK1 during fasting?
A. I'll discuss that later in the talk.
Q. Do ghrelin receptors colocalize with CCK or CB-1 receptors?
A. Yes, the covary in the same sort of way.
Q. The data showing that CCK modulates gene expression of vagal afferents, is that information from mRNA?
A. Yes, it was measured by in situ hybridization.
Q. Have you measured the protein yet?
A. Not yet.
Q. Do we know if gastric filling is correlated with CCK release, or is it causal? You could settle this in the human by simultaneously aspirating while filling. Is that something that is feasible?
A. You could, perhaps we should do that. It may not answer the fundamental question though, whether one is causing the other, or if they are just correlated.
Q. Is it known whether there is a distinction in lean or obese, in terms of CCK response?
A. I'm not sure about that.
Q. What about leptin? Gastric leptin might induce satiety.
A. I'm not sure how you really do a good leptin experiment in man. Most of us are leptin insensitive.