Excessive duodenal lipid-induced release of apoA-IV and CCK in GERD. - GreenMedInfo Summary
Duodenal lipid-induced symptom generation in gastroesophageal reflux disease: role of apolipoprotein A-IV and cholecystokinin.
Neurogastroenterol Motil. 2012 Apr ;24(4):350-e168. Epub 2012 Feb 2. PMID: 22300015
Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, the Netherlands. email@example.com
BACKGROUND: Duodenal lipid intensifies the perception of esophageal acid perfusion. Recently, we showed that genes implicated in lipid absorption were upregulated in the duodenum of fasting gastro-esophageal reflux disease (GERD) patients. This suggests that chylomicron production and secretion may be enhanced and, consequently, the release of apolipoprotein A-IV (apoA-IV), a chylomicron-derived signaling protein. ApoA-IV may stimulate release of cholecystokinin (CCK), an activator of vagal afferents. This study evaluated putative involvement of abnormal apoA-IV and CCK responses to lipid in GERD.
METHODS: Ten GERD patients and 10 healthy volunteers (HV) underwent duodenal perfusion with Intralipid 20%, 2 kcal min(-1) , for 60 min. Symptoms were scored, blood samples collected every 15 min during lipid perfusion and 15 min after discontinuation when duodenal biopsies were taken. Plasma and mucosalconcentrations of apoA-IV and CCK and transcript levels of 21 genes implicated in lipid absorption, differentially expressed under fasting conditions, were quantified.
KEY RESULTS: Heartburn (P = 0.003), abdominal discomfort (P = 0.037) and nausea (P = 0.008) only increased significantly during lipid infusion in GERD patients. Following lipid infusion mean mucosal apoA-IV concentration was lower in GERD patients compared with HV (P = 0.023), whereas plasma concentration tended to be elevated (P = 0.068). Mean mucosal CCK concentration was also lower in GERD patients (P = 0.009). Two genes, HIBADH and JTB, were upregulated in GERD patients (P = 0.008 and P = 0.038, respectively).
CONCLUSIONS & INFERENCES: Our results suggest excessive duodenal lipid-induced release of apoA-IV and CCK in GERD. We postulate that the resulting heightened activation of duodenal vagal afferents may underlie central sensitization, thereby increasing the perception of reflux events.