The intestinal lymph fistula model—a novel approach to study ghrelin secretion
- 1 March 2010
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Gastrointestinal and Liver Physiology
- Vol. 298 (3), G474-G480
- https://doi.org/10.1152/ajpgi.00367.2009
Abstract
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.Keywords
This publication has 41 references indexed in Scilit:
- GOAT links dietary lipids with the endocrine control of energy balanceNature Medicine, 2009
- Acyl and Total Ghrelin Are Suppressed Strongly by Ingested Proteins, Weakly by Lipids, and Biphasically by CarbohydratesJournal of Clinical Endocrinology & Metabolism, 2008
- Novel Ghrelin Assays Provide Evidence for Independent Regulation of Ghrelin Acylation and Secretion in Healthy Young MenJournal of Clinical Endocrinology & Metabolism, 2008
- Ghrelin octanoylation mediated by an orphan lipid transferaseProceedings of the National Academy of Sciences, 2008
- Orexigenic Hormone Ghrelin Attenuates Local and Remote Organ Injury after Intestinal Ischemia-ReperfusionPLOS ONE, 2008
- Exogenous ghrelin modulates release of pro-inflammatory and anti-inflammatory cytokines in LPS-stimulated macrophages through distinct signaling pathwaysSurgery, 2008
- Fasting and postprandial concentrations of GLP-1 in intestinal lymph and portal plasma: evidence for selective release of GLP-1 in the lymph systemAmerican Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2007
- Ghrelin promotes thymopoiesis during agingJCI Insight, 2007
- Differential Effects of High-fat and High-carbohydrate Content Isoenergetic Meals on Plasma Active Ghrelin Concentrations in Lean and Obese WomenHormone and Metabolic Research, 2004
- Intestinal absorption and metabolism of hydrocarbonsProgress in Lipid Research, 1989