LPS induces transient lipid accumulation and expression of ADRP in the liver through inhibition of fatty acid oxidation by downregulation of the PPARalpha-related transcriptional mechanism.

Background and Aim: A glucagon-like peptide-1 analog, liraglutide, has been reported to block inflammatory somatic pain. We hypothesized that liraglutide attenuates lipopolysaccharide (LPS)-induced and repeated water avoidance stress (WAS)-induced visceral hypersensitivity and tested the hypothesis in rats. Methods: The threshold of the visceromotor response induced by colonic balloon distention was measured to assess visceral sensation. Colonic permeability was determined in vivo by quantifying the absorbed Evans blue spectrophotometrically, which was instilled in the proximal colon for 15 min. The interleukin-6 level in colonic mucosa was also quantified using ELISA. Results: Subcutaneously injected LPS (1 mg/kg) reduced the visceromotor response threshold after 3 h. Liraglutide (300 μg/kg subcutaneously) at 15 h and 30 min before injecting LPS eliminated LPS-induced allodynia. It also blocked the allodynia induced by repeated water avoidance stress for 1 h for three consecutive days. Neither vagotomy nor naloxone altered the antinociceptive effect of liraglutide, but N G -nitro-L-arginine methyl ester, a nitric oxide synthesis inhibitor, blocked it. LPS increased colonic permeability and the interleukin-6 level, and the analog significantly inhibited these responses. Conclusions: This study suggests that liraglutide blocked LPS-induced visceral allodynia, which may be a nitric oxide-dependent response, and was probably mediated by inhibiting pro-inflammatory cytokine production and attenuating the increased gut permeability. Because the LPS-cytokine system is considered to contribute to altered visceral sensation in irritable bowel syndrome, these results indicate the possibility that liraglutide can be useful for treating this disease.

Peripheral CRF stimulates gastric contractions through CRF(1). CRF(2) activation inhibits the response induced by CRF, suggesting that CRF(2) may have a modulatory action to CRF(1) signaling in gastric motor activity.

Running head; Stress and gastric motility 2 Abstract Background. Stress alters gastrointestinal motility through central and

Increasing evidence has indicated that brain orexin plays a vital role in the regulation of gastrointestinal physiology such as gastric secretion, gastric motility and pancreatic secretion. However, little is known whether orexin in the brain is involved in the physiology of the lower gastrointestinal tract. The aim of this study was therefore to elucidate whether orexin-A in the brain is involved in the regulation of colonic motility. In this study, we measured fecal pellet output and recorded intraluminal colonic pressure waves in freely moving conscious rats to evaluate the effects of central orexin-A on colonic motor functions. Intracisternal but not intraperitoneal injection of orexin-A dose-dependently (1-10 μg) increased fecal pellet output. Findings obtained from manometric recordings revealed that intracisternal administration of orexin-A at a dose of 10 μg significantly enhanced colonic motor contractions. These results suggest for the first time that orexin-A acts centrally in the brain to enhance fecal pellet output and stimulate colonic motility in conscious rats. The present study would furthermore support our hypothesis that orexin-A in the brain may be an important candidate as a mediator of the cephalic phase gut stimulation including stimulated colonic motility in addition to well known physiological response such as stimulation of gastric acid and pancreatic acid secretion, and gastric motility.