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HORMONES AND SIGNALING

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

¹Center for Ulcer Research and Education: Digestive Diseases Research Center, Division of Digestive Diseases, ²Center for Human Nutrition, and ³Center for Neurovisceral Sciences and Women's Health, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles; ⁴Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California; and ⁵Department of Nutrition, University of Montréal, Montréal, Québec, Canada

Submitted 17 November 2005 ; accepted in final form 25 April 2006

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-1 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-1 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.

insulin; food intake; gastric emptying; urocortin 1; prostaglandins; interleukin-1; lipopolysaccharide

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