NamKoong Cherl, Kim Min Sun, Jang Byeong-Tak, Lee Young Hee, Cho Young-Min, Choi Hyung Jin
Functional Neuroanatomy of Metabolism Regulation Laboratory, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea; BK21Plus Biomedical Science Project, Seoul National University College of Medicine, Seoul, Republic of Korea; Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Functional Neuroanatomy of Metabolism Regulation Laboratory, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea; BK21Plus Biomedical Science Project, Seoul National University College of Medicine, Seoul, Republic of Korea.
Biochem Biophys Res Commun. 2017 Aug 19;490(2):247-252. doi: 10.1016/j.bbrc.2017.06.031. Epub 2017 Jun 10.
Glucagon-like peptide-1 amide (GLP-1) and gastric inhibitory polypeptide (GIP) are incretin hormones regulating energy metabolism. GLP-1 and GIP combination is suggested as a promising therapeutic strategy for treatment of obesity and diabetes. However, the neuronal mechanisms are not yet investigated. In the present study, we investigated the role of central GLP-1 and GIP in regulation of body weight homeostasis. The effect of GLP-1 with GIP on food intake, body weight, locomotor activity were determined following intracerebroventricular (ICV) administration of GLP-1 and/or GIP in mice. ICV administration of low dose GLP-1 (0.3 nmol) and GIP (1 and 3 nmol) did not change food intake. However, ICV administration of higher doses GLP-1 (1 and 3 nmol) and GIP (6 nmol) significantly decreased food intake and body weight. To investigate the synergic effect of ICV GLP-1 and GIP, subeffective dose GLP-1 (0.3 nmol) and subeffective dose GIP (1 nmol) were chosen for further co-administration study. ICV co-administration of GLP-1 and GIP significantly decreased food intake, body weight and drinking. ICV co-administration of GLP-1 and GIP significantly increased neuronal activation and pro-opiomelanocortin (POMC) expression in hypothalamic arcuate nucleus. The neuronal activation and POMC expression were observed in two distinct neuronal populations. These results provide neuronal mechanisms supporting the development of GLP-1 and GIP combination therapeutics for treatment of obesity and diabetes.
胰高血糖素样肽-1酰胺（GLP-1）和胃抑制多肽（GIP）是调节能量代谢的肠促胰岛素激素。GLP-1与GIP联合使用被认为是治疗肥胖症和糖尿病的一种有前景的治疗策略。然而，其神经机制尚未得到研究。在本研究中，我们研究了中枢GLP-1和GIP在体重稳态调节中的作用。在小鼠脑室内（ICV）注射GLP-1和/或GIP后，测定GLP-1与GIP对食物摄入量、体重、运动活动的影响。脑室内注射低剂量GLP-1（0.3 nmol）和GIP（1和3 nmol）不会改变食物摄入量。然而，脑室内注射较高剂量的GLP-1（1和3 nmol）和GIP（6 nmol）可显著降低食物摄入量和体重。为了研究脑室内GLP-1和GIP的协同作用，选择亚有效剂量的GLP-1（0.3 nmol）和亚有效剂量的GIP（1 nmol）进行进一步的联合给药研究。脑室内联合注射GLP-1和GIP可显著降低食物摄入量、体重和饮水量。脑室内联合注射GLP-1和GIP可显著增加下丘脑弓状核的神经元激活和阿黑皮素原（POMC）表达。在两个不同的神经元群体中观察到了神经元激活和POMC表达。这些结果为开发用于治疗肥胖症和糖尿病的GLP-!和GIP联合疗法提供了神经机制支持。
