Lipopolysaccharide differentially decreases plasma acyl and desacyl ghrelin levels in rats: potential role of the circulating ghrelin-acylating enzyme GOAT.
Bacterial lipopolysaccharide (LPS) in rodents is an established model for studying innate immune responses to gram-negative bacteria and mimicking symptoms of infections including reduced food intake associated with decreased circulating total ghrelin levels. The ghrelin-acylating enzyme, ghrelin-O-acyltransferase (GOAT) involved in the formation of acyl ghrelin (AG) was recently identified. We investigated changes in circulating AG, desacyl ghrelin (DG) and GOAT induced by intraperitoneal LPS (100 microg/kg) and associated changes in food intake. Plasma AG and total ghrelin were assessed by radioimmunoassay, GOAT protein by Western blot and mRNA by RT-qPCR. DG was derived from total minus AG. Plasma AG and DG were decreased at 2, 5 and 7 h (p<0.01) post-injection compared to vehicle and recovered at 24 h. At 2 h there was a significantly greater decrease of AG (-53%) than DG (-28%) resulting in a decreased AG/DG ratio (1:5, p<0.01), which thereafter returned to pre-injection values (1:3). This altered ratio was associated with a 38% decrease in plasma GOAT protein compared to vehicle (p<0.001), whereas gastric GOAT protein was slightly increased by 10% (p<0.05). GOAT mRNA expression was unchanged. Food intake was reduced by 58% measured during the 1.5-2 h period post-LPS injection. Decreased plasma AG and DG preceded the rise in rectal temperature and blood glucose that peaked at 7 h. These data indicate that LPS induces a long-lasting reduction of AG and DG levels that may have a bearing with the decrease in food intake. The faster drop in AG than DG within 2 h is associated with reduced circulating GOAT.
Stengel
Andreas
A
CURE/Digestive Diseases Research Center, Center for Neurobiology of Stress, Department of Medicine, Digestive Diseases Division at the University of California Los Angeles, and VA Greater Los Angeles Health Care System, Los Angeles, CA 90073, USA.
Goebel
Miriam
M
Wang
Lixin
L
Reeve
Joseph R
JR
Taché
Yvette
Y
Lambrecht
Nils W G
NW
D000210:Acute-Phase Reaction / Q000503:physiopathology; D000217:Acyltransferases / Q000097:blood* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001069:Appetite Regulation; D001786:Blood Glucose / Q000032:analysis; D015153:Blotting, Western; D001831:Body Temperature; D015536:Down-Regulation; D005753:Gastric Mucosa / Q000378:metabolism; D054439:Ghrelin / Q000097:blood*; D016481:Helicobacter Infections / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D001786:Blood Glucose; D054439:Ghrelin; D008070:Lipopolysaccharides; D012333:RNA, Messenger; C422650:ghrelin, des-n-octanoyl; D000217:Acyltransferases; C534462:ghrelin O-acyltransferase, rat