title: Lipopolysaccharide increases gastric and circulating NUCB2/nesfatin-1 concentrations in rats.
abstract: Bacterial lipopolysaccharide (LPS) is an established animal model to study the innate immune response to Gram-negative bacteria mimicking symptoms of infection including reduction of food intake. LPS decreases acyl ghrelin associated with decreased concentrations of circulating ghrelin-O-acyltransferase (GOAT) likely contributing to the anorexigenic effect. We also recently described the prominent expression of the novel anorexigenic hormone, nucleobindin2 (NUCB2)/nesfatin-1 in gastric X/A-like cells co-localized with ghrelin in different pools of vesicles. To investigate whether LPS would affect gastric and circulating NUCB2/nesfatin-1 concentration, ad libitum fed rats were equipped with an intravenous (iv) catheter. LPS was injected intraperitoneally (ip, 100μg/kg) and blood was withdrawn before and at 2, 5, 7 and 24h post injection and processed for NUCB2/nesfatin-1 radioimmunoassay. Gastric corpus was collected to measure NUCB2 mRNA expression by RT-qPCR and NUCB2/nesfatin-1 protein concentration by Western blot. Injection of LPS increased plasma NUCB2/nesfatin-1 concentrations by 43%, 78% and 62% compared to vehicle at 2h, 5h and 7h post injection respectively (p<0.05) and returned to baseline at 24h. The plasma NUCB2/nesfatin-1 increase at 2h was associated with increased corpus NUCB2 mRNA expression (p<0.01), whereas NUCB2 mRNA was not detectable in white blood cells. Likewise, gastric NUCB2 protein concentration was increased by 62% after LPS compared to vehicle (p<0.01). These data show that gastric NUCB2 production and release are increased in response to LPS. These changes are opposite to those of ghrelin in response to LPS supporting a differential gastric regulation of NUCB2/nesfatin-1 and ghrelin expression derived from the same cell by immune challenge.
authors.affiliation: CURE/Digestive Diseases Research Center, Center for Neurobiology of Stress, Department of Medicine, Digestive Diseases Division, University of California Los Angeles, VA Greater Los Angeles Health Care System, CA 90073, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Stengel
authors.forename: Miriam
authors.initials: M
authors.lastname: Goebel-Stengel
authors.forename: Janusz
authors.initials: J
authors.lastname: Jawien
authors.forename: Peter
authors.initials: P
authors.lastname: Kobelt
authors.forename: Yvette
authors.initials: Y
authors.lastname: Taché
authors.forename: Nils W G
authors.initials: NW
authors.lastname: Lambrecht
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000097:blood / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000097:blood / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D054439:Ghrelin / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000097:blood / Q000378:metabolism*; D000080866:Nucleobindins; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D054439:Ghrelin; D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins; D012333:RNA, Messenger; C422650:ghrelin, des-n-octanoyl