LPS inhibits fasted plasma ghrelin levels in rats: role of IL-1 and PGs and functional implications.
LPS injected intraperitoneally decreases fasted plasma levels of ghrelin at 3 h postinjection in rats. We characterized the inhibitory action of LPS on plasma ghrelin and whether exogenous ghrelin restores LPS-induced suppression of food intake and gastric emptying in fasted rats. Plasma ghrelin and insulin and blood glucose were measured after intraperitoneal injection of LPS, intravenous injection of IL-1beta and urocortin 1, and in response to LPS under conditions of blockade of IL-1 or CRF receptors by subcutaneous injection of IL-1 receptor antagonist (IL-1Ra) or astressin B, respectively, and prostaglandin (PG) synthesis by intraperitoneal indomethacin. Food intake and gastric emptying were measured after intravenous injection of ghrelin at 5 h postintraperitoneal LPS injection. LPS inhibited the elevated fasted plasma ghrelin levels by 47.6 +/- 4.9%, 58.9 +/- 3.3%, 74.4 +/- 2.7%, and 48.9 +/- 8.7% at 2, 3, 5, and 7 h postinjection, respectively, and values returned to preinjection levels at 24 h. Insulin levels were negatively correlated to those of ghrelin, whereas there was no significant correlation between glucose and ghrelin. IL-1Ra and indomethacin prevented the first 3-h decline in ghrelin levels induced by LPS, whereas astressin B did not. IL-1beta inhibited plasma ghrelin levels, whereas urocortin 1 had no influence. Ghrelin injected intravenously prevented an LPS-induced 87% reduction of gastric emptying and 61% reduction of food intake. These data showed that IL-1 and PG pathways are part of the early mechanisms by which LPS suppresses fasted plasma ghrelin and that exogenous ghrelin can normalize LPS-induced-altered digestive functions.
Wang
Lixin
L
CURE Bldg. 115, Rm. 117B, 11301 Wilshire Blvd., Los Angeles, CA 90073, USA.
Basa
Nicole R
NR
Shaikh
Almaas
A
Luckey
Andrew
A
Heber
David
D
St-Pierre
David H
DH
Taché
Yvette
Y
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005215:Fasting / Q000097:blood*; D005247:Feeding Behavior / Q000187:drug effects; D005746:Gastric Emptying / Q000187:drug effects; D054439:Ghrelin; D007213:Indomethacin; D007328:Insulin / Q000097:blood; D007375:Interleukin-1 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D036361:Peptide Hormones / Q000097:blood*; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D054832:Urocortins
D001786:Blood Glucose; D054439:Ghrelin; D007328:Insulin; D007375:Interleukin-1; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D036361:Peptide Hormones; D011453:Prostaglandins; D054832:Urocortins; C120841:astressin B; D003346:Corticotropin-Releasing Hormone; D007213:Indomethacin