The intestinal lymph fistula model--a novel approach to study ghrelin secretion.
The orexigenic hormone ghrelin is secreted from the stomach and has been implicated in the regulation of energy and glucose homeostasis. We hypothesized that ghrelin, like other gastrointestinal (GI) hormones, is present in intestinal lymph, and sampling this compartment would provide advantages for studying ghrelin secretion in rodents. Blood and lymph were sampled from catheters in the jugular vein and mesenteric lymph duct before and after intraduodenal (ID) administration of isocaloric Ensure, dextrin, or Liposyn meals or an equal volume of saline in conscious Sprague-Dawley rats. Total ghrelin levels were measured using an established radioimmunoassay. Acyl and des-acyl ghrelin were measured using two-site ELISA. Fasting ghrelin levels in lymph were significantly higher than in plasma (means +/- SE: 3,307.9 +/- 272.9 vs. 2,127.1 +/- 115.0 pg/ml, P = 0.004). Postingestive acyl and des-acyl ghrelin levels were also significantly higher, whereas the ratio of acyl:des-acyl ghrelin was similar in lymph and plasma (0.91 +/- 0.28 vs. 1.20 +/- 0.36, P = 0.76). The principle enzymes responsible for deacylation of ghrelin were lower in lymph than in plasma. Following ID Ensure, maximum ghrelin suppression occurred at 2 h in lymph compared with at 1 h in plasma. The return of suppressed ghrelin levels to baseline was also delayed in lymph. Similarly, dextrin also induced significant suppression of ghrelin (two-way ANOVA: P = 0.02), whereas Liposyn did not (P = 0.32). On the basis of these findings, it appears that intestinal lymph, which includes drainage from the interstitium of the GI mucosa, is enriched in ghrelin. Despite reduced deacylating activity in lymph, there is not a disproportionate amount of acyl ghrelin in this pool. The postprandial dynamics of ghrelin are slower in lymph than plasma, but the magnitude of change is greater. Assessing ghrelin levels in the lymph may be advantageous for studying its secretion and concentrations in the gastric mucosa.
Tong
Jenny
J
Departments of Medicine, University of Cincinnati, Ohio, 45267-0547, USA. jenny.tong@uc.edu
Tschöp
Matthias H
MH
Aulinger
Benedikt A
BA
Davis
Harold W
HW
Yang
Qing
Q
Liu
Jianhua
J
Gaylinn
Bruce D
BD
Thorner
Michael O
MO
D'Alessio
David
D
Tso
Patrick
P
D000107:Acetylation; D000818:Animals; D002091:Butyrylcholinesterase / Q000097:blood / Q000378:metabolism; D043182:Carboxylesterase / Q000097:blood / Q000378:metabolism; D003912:Dextrins / Q000008:administration & dosage / Q000494:pharmacology; D019422:Dietary Sucrose / Q000008:administration & dosage / Q000494:pharmacology; D004655:Emulsions; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage / Q000494:pharmacology; D005402:Fistula; D005526:Food, Formulated; D054439:Ghrelin / Q000031:analogs & derivatives / Q000032:analysis* / Q000097:blood / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects / Q000601:surgery; D054709:Lecithins; D008196:Lymph / Q000737:chemistry / Q000378:metabolism*; D042601:Lymphatic Vessels / Q000601:surgery; D008297:Male; D023421:Models, Animal; D019518:Postprandial Period / Q000502:physiology; D020033:Protein Isoforms / Q000097:blood / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012450:Safflower Oil; D013024:Soybean Oil
D003912:Dextrins; D019422:Dietary Sucrose; D004655:Emulsions; D005217:Fat Emulsions, Intravenous; D054439:Ghrelin; D054709:Lecithins; D020033:Protein Isoforms; C031435:safflower oil, soybean oil, lecithin emulsion; C082131:Ensure formulated food; D013024:Soybean Oil; D012450:Safflower Oil; D043182:Carboxylesterase; D002091:Butyrylcholinesterase