Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, C057

Oral Communications

High fat diet abolishes the inhibitory effect of centrally administered nesfatin-1 on gastric emptying rate: role of GLP-1 and CCK receptors

Z. N. Özdemir Kumral1, S. Arabaci Tamer1, T. Koyuncuoglu1, B. Yegen1

1. Physiology, Marmara University, Istanbul, Turkey.

Obesity was shown to be associated with facilitated gastric emptying, which could either be the cause or the consequence of obesity.1 The anorexigenic neuropeptide, nesfatin-1 (NES-1), when given centrally, suppresses gastric contractions and gastric motility2. High fat diet (HFD) in mice was shown to decrease plasma NES-1 levels.3 However, the impact of HFD on NES-1 induced inhibition of gastric motility, and the peripheral mechanisms underlying the inhibitory effect of NES-1 on gastric emptying were not elucidated yet. In the present study, the involvement of cholecystokinin (CCK)-1, CCK-2 and glucagon-like peptide-1 (GLP-1) receptors in non-caloric liquid emptying and the effect of HFD on NES-1-induced alterations in gastric emptying were investigated. Male Sprague-Dawley rats (10-week-old) were fed with normal diet (ND, 2.7% fat, n=8) or HFD (45% fat, n=8) for 8 weeks. Under ketamine and chlorpromazine (100 and 10 mg/kg,intraperitoneally) anaesthesia, a Gregory cannula was installed in the gastric corpus, and one week later an intracerebroventricular (icv) cannula was placed. After 2 weeks, gastric emptying (GE) rate of saline was determined from the volume and absorbance of fluid recovered 5 min after instillation of phenol red-added saline into the stomach. Gastric emptying was commenced 5 min after icv NES-1 (0.05 µg/0.5 µl) or saline (0.5 µl) injection, which were preceded with subcutaneous injections of either saline or GLP-1 receptor antagonist exendin 9-39 (30 µg/kg) or CCK-1 receptor antagonist devazepide (1 mg/kg) or gastrin/CCK-2 receptor antagonist YM022 (1 mg/kg). At the end of the experiments, verification of icv cannula placement was made using methylene blue. In ND-receiving groups, central NES-1 administration significantly decreased gastric emptying rate (2.62 ± 0.02 ml/5min) compared to icv saline administration (3.06 ± 0.08 ml/5min). None of the antagonists changed the GE rate in icv saline administered rats, but NES-1-induced delay in GE rate was abolished by GLP-1 (3.06 ± 0.13 ml/5 min), CCK-1 (3.25 ± 0.13 ml/5 min, p <0.05) and CCK-2 (3.35 ± 0.13 ml/5 min, p <0.05) receptor antagonist. On the other hand, GE rates in HFD-fed rats were not different among centrally NES-1 (2.95 ± 0.26 ml/5 min) or saline (2.95 ± 0.26 ml/5 min) injected ones, and were similar to saline-injected ND-fed rats, while antagonists did not alter GE rates of HFD-fed rats injected icv with NES-1 or saline. The findings of current study demonstrate that NES-1-induced delay in gastric emptying was mediated via the involvement of GLP-1, CCK-1 and CCK-2 receptors, while this inhibitory effect of NES-1 on gastric emptying rate was not evident when rats were on HFD, suggesting that prolonged consumption of HFD abolishes the inhibitory role of anorexigenic nesfatin-1 on gastric motility and facilitates gastric emptying.

Where applicable, experiments conform with Society ethical requirements