LPS inhibits fasted plasma ghrelin levels in rats: role of IL-1 and PGs and functional implications

• Published in: American journal of physiology: Gastrointestinal and liver physiology 2006-10, Vol.291 (4), p.G611-G620
• Main Authors: Wang, Lixin, Basa, Nicole R, Shaikh, Almaas, Luckey, Andrew, Heber, David, St-Pierre, David H, Taché, Yvette
• Format: Article
• Language: English
• Subjects: Animals; Blood Glucose - drug effects; Corticotropin-Releasing Hormone - pharmacology; Dose-Response Relationship, Drug; Fasting - blood; Feeding Behavior - drug effects; Gastric Emptying - drug effects; Ghrelin; Indomethacin; Insulin - blood; Interleukin-1 - metabolism; Lipopolysaccharides - pharmacology; Male; Peptide Fragments - pharmacology; Peptide Hormones - blood; Prostaglandins - metabolism; Rats; Rats, Sprague-Dawley; Urocortins
• ISSN: 0193-1857; 1522-1547
• DOI: 10.1152/ajpgi.00533.2005

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.