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

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

K Coveleskie  1 , L A Kilpatrick  1   2   3 , A Gupta  1   2   3 , J Stains  1 , L Connolly  3 , J S Labus  1   2   3 , C Sanmiguel  1   2   3 , E A Mayer  1   2   4   3
Affiliations

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

K Coveleskie et al. Obes Sci Pract. .

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.

Keywords: Brain; GLP‐1; hunger; obesity.

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Figures

Figure 1
Figure 1
Basic scan day protocol. Subjects were brought in after at least 8 h of fasting. Scans were done both pre‐subcutaneous and post‐subcutaneous injection of either drug or saline placebo. After scanning, subjects were given a meal. Blood draws and questionnaires were given before scanning and 35 and 60 min after injection.
Figure 2
Figure 2
Calorie consumption of lean versus obese subjects of a post‐scan meal. Trends show that both lean and obese groups consumed fewer calories on the day of the exenatide injection versus the placebo day and that the obese group consumed more calories on both days.
Figure 3
Figure 3
Functional connectivity analysis of nucleus of the solitary tract (NTS) with thalamus and hypothalamus in obese compared with lean. (A) The obese group showed increased left NTS functional connectivity with the thalamus and the hypothalamus and (B) compared with the lean group showed increased right NTS functional connectivity with the left thalamus.
Figure 4
Figure 4
Nucleus of the solitary tract (NTS) functional connectivity correlation analysis with calorie consumption and hunger. (A) All subjects together showed a positive correlation between calories consumed of a meal and functional connectivity of the right NTS with the right hypothalamus and left thalamus. (B) At baseline before scanning, the lean group showed a greater correlation between hunger and right NTS functional connectivity with the left thalamus. After exenatide injection (versus placebo), (C) all subjects combined had a correlation between hunger and right NTS functional connectivity with the right hypothalamus and (D) the obese group had a greater correlation between hunger and right NTS functional connectivity with the left thalamus.
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