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胰高血糖素样肽-1类似物艾塞那肽对有肥胖和无肥胖女性基于孤束核的网络内功能连接的影响。

The effect of the GLP-1 analogue Exenatide on functional connectivity within an NTS-based network in women with and without obesity.

作者信息

Coveleskie K, Kilpatrick L A, Gupta A, Stains J, Connolly L, Labus J S, Sanmiguel C, Mayer E A

机构信息

G Oppenheimer Center for Neurobiology of Stress and Resilience, Ingestive Behavior & Obesity Program UCLA Los Angeles CA USA.

Vatche and Tamar Manoukin Division of Digestive Diseases UCLA Los Angeles CA USA.

出版信息

Obes Sci Pract. 2017 Nov 10;3(4):434-445. doi: 10.1002/osp4.124. eCollection 2017 Dec.

DOI:10.1002/osp4.124
PMID:29259802
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5729499/
Abstract

OBJECTIVE

The differential effect of GLP-1 agonist Exenatide on functional connectivity of the nucleus tractus solitaries (NTS), a key region associated with homeostasis, and on appetite-related behaviours was investigated in women with normal weight compared with women with obesity.

METHODS

Following an 8-h fast, 19 female subjects (11 lean, 8 obese) participated in a 2-d double blind crossover study. Subjects underwent functional magnetic resonance imaging at fast and 30-min post subcutaneous injection of 5 μg of Exenatide or placebo. Functional connectivity was examined with the NTS. Drug-induced functional connectivity changes within and between groups and correlations with appetite measures were examined in a region of interest approach focusing on the thalamus and hypothalamus.

RESULTS

Women with obesity reported less hunger after drug injection. Exenatide administration increased functional connectivity of the left NTS with the left thalamus and hypothalamus in the obese group only and increased the correlation between NTS functional connectivity and hunger scores in all subjects, but more so in the obese.

CONCLUSIONS

Obesity can impact the effects of Exenatide on brain connectivity, specifically in the NTS and is linked to changes in appetite control. This has implications for the use of GLP-1 analogues in therapeutic interventions.

摘要

目的

研究胰高血糖素样肽-1（GLP-1）激动剂艾塞那肽对体重正常女性和肥胖女性孤束核（NTS）功能连接性及食欲相关行为的不同影响，NTS是与内稳态相关的关键区域。

方法

禁食8小时后，19名女性受试者（11名体重正常者，8名肥胖者）参与了一项为期2天的双盲交叉研究。受试者在禁食状态下以及皮下注射5μg艾塞那肽或安慰剂后30分钟接受功能磁共振成像检查。采用NTS检测功能连接性。采用感兴趣区域法，重点关注丘脑和下丘脑，研究药物诱导的组内和组间功能连接性变化以及与食欲指标的相关性。

结果

肥胖女性在注射药物后报告饥饿感减轻。仅在肥胖组中，艾塞那肽给药增加了左侧NTS与左侧丘脑和下丘脑之间的功能连接性，并增加了所有受试者中NTS功能连接性与饥饿评分之间的相关性，但在肥胖者中更为明显。

结论

肥胖会影响艾塞那肽对大脑连接性的作用，特别是在NTS，并且与食欲控制的变化有关。这对GLP-1类似物在治疗干预中的应用具有启示意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/820e/5729499/06474855c562/OSP4-3-434-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/820e/5729499/61f3faf49d42/OSP4-3-434-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/820e/5729499/fcb7f43f17c5/OSP4-3-434-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/820e/5729499/054224195fb9/OSP4-3-434-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/820e/5729499/06474855c562/OSP4-3-434-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/820e/5729499/61f3faf49d42/OSP4-3-434-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/820e/5729499/fcb7f43f17c5/OSP4-3-434-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/820e/5729499/054224195fb9/OSP4-3-434-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/820e/5729499/06474855c562/OSP4-3-434-g004.jpg

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