Sa1403 Upper Gastrointestinal Symptoms After Laparoscopic Sleeve Gastrectomy

Abstract

occur at a higher frequency in ileal segments of refed guinea pigs (p=0.028). Ca2+-imaging in longitudinal muscle myenteric plexus preparations (N=3-4) revealed elevated responses to orexigenic ghrelin in fasted animals (p=0.013), but the percentage of responders to anorexigenic CCK-8 was higher in refed animals (p<0.001). High K+-evoked Ca2+-peaks were consistently higher in refed animals (p<0.001), suggestive of a hyperexcitable state. We investigated whether a humoral factor was involved by exposing cultured myenteric neurons (N=3-6) to fasted or refed guinea pig serum and found that the cells acutely exposed to refed serum displayed a higher Ca2+-peak (p<0.001) and more neurons became spontaneously active (p<0.001). Interestingly, we found that ghrelin-responses were higher in cells incubated with fasted serum (p=0.023), whereas serotonin-responses proved to be higher in cells incubated with refed serum (p=0.005). Centrifugal ultrafiltration (MW cutoff 3K) removed a feeding state-independent along with a feeding state-dependent factor from the serum, the latter reverting amplitudes of refed serumto fasted serum-responses (N=3). Since glycemia in refed guinea pigs was almost 3 times as high as in fasted guinea pigs, we tested whether these glucose-levels play a role in the fasted-refed differences in neuronal Ca2+-signaling (N=3). We found that ghrelin evoked higher amplitudes in cells incubated with fasted glucose-levels (p<0.001), whereas CCK-8 (p=0.005), serotonin (p= 0.006) and high K+ (p<0.001) evoked higher responses in cells incubated with refed glucoselevels. These observations indicate that the feeding status of an animal remains imprinted ex-vivo and humoral feeding state-related factors are implicated. Although the molecular link with hyperactivity is not entirely elucidated yet, we found that a glucose-dependent pathway is involved, probably in combination with other factors. Although responses in the refed state are generally increased, the reduced neuronal responses to ghrelin prove that the effect is signaling pathway-specific and suggests feeding state-related differential tuning of excitability.