Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCB191

Poster Communications

GLP-2 inhibits food intake in DMH and NTS

H. Sun1,2,3, K. Meng3, L. Hou3, L. Shang4, J. Yan1,2,3

1. Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, China. 2. Research Center of Stomatology College, Xi'an Jiaotong University, Xi'an, China. 3. Department of Physiology and Pathophysiology, Xi'an Jiaotong University Health Science Center, Xi'an, China. 4. Faculty of Life Sciences, University of Bradford, Bradford, United Kingdom.

GLP-2, expressed in the hypothalamus (the dorsomedial hypothalamic nucleus, DMH and arcuate nucleus, ARC) and in the brain stem (the dorsal motor nucleus of vagus nerve, DMV and the parabrachial nucleus, PBN) and produced from PPG neurons in the brain stem the nucleus tractus solitarius (NTS), is the key signal for the brain and pancreas to control energy balance (1, 2). Previous studies show that GLP-2 inhibits food intake in CNS by GLP-2 infusion into lateral ventricle and 4th ventricle (3). However, which exact central nerve nuclei involves GLP-2 central effects on food intake is currently unknown. In this study, we examined the effect of GLP-2 on food intake in DMH and NTS at free- or fasted-feeding (16h) rats. Male SD rats, from the Medical Experimental Animal Center of Xi'an Jiaotong University, with stainless steel cannulas implanted unilaterally into the DMH and NTS were used. All protocols were complied with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH No. 80-23). Rats were anaesthetized by pentobarbital sodium and isoflurane before the surgical operation and then given injection GLP-2. After 7 days recovery, experiments began and lasted for 11 days under the count-balance design. Food intake were recorded at different time point. Values are means ± S.E.M., compared by two-way ANOVA. Subsequent comparisons between groups used post-hoc Bonferroni tests. Our data showed that compared to the control (0ug/0.5ul), 10ug/0.5ul GLP-2 injection into DMH after 4h at free-feeding could inhibit food intake about 19.6% (3.73 ± 0.66 g vs 3.00 ± 0.66 g, n=8, p < 0.05), and GLP-2 injection with same concentration into DMH after 6h could inhibit food intake by 46.1% at fasted-feeding (14.1 ± 1.6 g vs 7.6 ± 1.6 g, n=8, p < 0.05). These food inhibiting effects can be blocked by 10ug/0.5ul Extendin 9-39 after GLP-2 injection 6h (Saline + GLP-2 vs Extendin + GLP-2: 7.3 ± 2.3 g vs 10.1 ± 0.9 g, n=8, p < 0.05) or by 0.5nmol/0.5ul SHU9119 after GLP-2 injection 24h (Saline + GLP_2 vs SHU9119 + GLP-2: 12.65 ± 3.7 g vs 24.2 g ± 3.7 g, n=8, p < 0.05). While 10ug/0.5ul GLP-2 injection into NTS could also inhibit food intake by 32.3% after injection 6h at fasted-feeding (0ug/0.5ul vs 10ug/0.5ul: 11.23 ± 3.6 g vs 7.6 ± 2.6 g, n=6, p < 0.05) but could not inhibit food intake at free-feeding status (0ug/0.5ul vs 10ug/0.5ul: 1.43 ± 0.8 vs 1.16 ± 0.26, p > 0.05). These food inhibiting effects can also be blocked by Extendin 9-39 with same concentration after GLP-2 injection 24h (Saline + GLP-2 vs Extendin + GLP-2 : 14.73 ± 2.5 g vs 22.10 ± 2.8 g, n=6, p < 0.05) but not by 0.5nmol/0.5ul SHU9119 after GLP-2 injection 24h (Saline + GLP-2 vs SHU9119 + GLP-2: 22.2 ± 3.75 vs 18.45 ± 2.28 g, p > 0.05). These data suggested that GLP-2 food inhibiting effect can happen in both NTS and DMH. Future works will focus on the underlying mechanism of the GLP-2 on feeding behavior between DMH and NTS circle.

Where applicable, experiments conform with Society ethical requirements