Diabetes Metab J. 2020;44(2):248-259.

Glucagon-Like Peptide-1 Receptor Agonist Differentially Affects Brain Activation in Response to Visual Food Cues in Lean and Obese Individuals with Type 2 Diabetes Mellitus.

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제1저자 배재현, 최형진 · 교신저자 조영민

PMID 31701698 PMC7188972 DOI 10.4093/dmj.2019.0018 IF 8.2 내분비대사내과

소속 (10)

Department of Medicine, Seoul National University College of Medicine, Seoul, Korea.
Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea.
Department of Anatomy, Seoul National University College of Medicine, Seoul, Korea.
Neuroscience Research Institute, Seoul National University, Seoul, Korea.
Wide River Institute of Immunology, Seoul National University, Seoul, Korea.
Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, Korea.
Institute of Human Behavioral Medicine, Seoul National University Medical Research Center, Seoul, Korea.
Department of Internal Medicine, Cheju Halla General Hospital, Jeju, Korea.
Department of Psychiatry, Seoul National University College of Medicine, Seoul, Korea.
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. ymchomd@snu.ac.kr.

Abstract

BACKGROUND To investigate the effects of a glucagon-like peptide-1 receptor agonist on functional brain activation in lean and obese individuals with type 2 diabetes mellitus (T2DM) in response to visual food cues.

METHODS In a randomized, single-blinded, crossover study, 15 lean and 14 obese individuals with T2DM were administered lixisenatide or normal saline subcutaneously with a 1-week washout period. We evaluated brain activation in response to pictures of high-calorie food, low-calorie food, and nonfood using functional magnetic resonance imaging and measured appetite and caloric intake in participants who were given access to an ad libitum buffet.

RESULTS Obese individuals with T2DM showed significantly greater activation of the hypothalamus, pineal gland, parietal cortex (high-calorie food vs. low-calorie food, P<0.05), orbitofrontal cortex (high-calorie food vs. nonfood, P<0.05), and visual cortex (food vs. nonfood, P<0.05) than lean individuals with T2DM. Lixisenatide injection significantly reduced the functional activation of the fusiform gyrus and lateral ventricle in obese individuals with T2DM compared with that in lean individuals with T2DM (nonfood vs. high-calorie food, P<0.05). In addition, in individuals who decreased their caloric intake after lixisenatide injection, there were significant interaction effects between group and treatment in the posterior cingulate, medial frontal cortex (high-calorie food vs. low-calorie food, P<0.05), hypothalamus, orbitofrontal cortex, and temporal lobe (food vs. nonfood, P<0.05).

CONCLUSION Brain responses to visual food cues were different in lean and obese individuals with T2DM. In addition, acute administration of lixisenatide differentially affected functional brain activation in these individuals, especially in those who decreased their caloric intake after lixisenatide injection.

Keywords

AppetiteBrainDiabetes mellitus, type 2Energy intakeFunctional neuroimagingGlucagon-like peptide 1LixisenatideMagnetic resonance imagingObesity

Figures

**Fig. 1** Study design and procedure. Fifteen lean and 14 obese individuals with type 2 diabetes mellitus were studied in a randomized, single-blinded, crossover study. (A) The study participants were randomly assigned to either the lixisenatide or saline injection group after an overnight fast. After administration of the injection, the brain responses to visual food cues were evaluated using functional magnetic resonance imaging (fMRI). After the fMRI session, the participants were given access to an *ad libitum* buffet to measure caloric intake. Appetite surveys were taken before the injection, after the fMRI session, and after the *ad libitum* buffet. One week apart, the participants were switched to the other condition group and performed the same procedure. (B) fMRI paradigm. One run consisted of six blocks of pictures that included high-calorie food, low-calorie food, and nonfood contents. Each type of picture was presented in a block with seven other pictures for 21 seconds and were shown twice in each run. The blocks were separated by 9 seconds of a black background with a white fixation cross. Each fMRI session had two runs of blocks with different orders to prevent the sequence effect. MR, magnetic resonance; T1, T1-weighted; DTI, diffusion tensor imaging.

**Fig. 2** Differences in brain responses to visual food cues in lean and obese individuals with type 2 diabetes mellitus (T2DM). (A) Activation of the hypothalamus and pineal gland in response to viewing high-calorie food pictures (high-calorie food vs. low-calorie food). (B) Activation of the parietal cortex in response to viewing low-calorie food pictures (low-calorie food vs. high-calorie food). (C) Activation of the orbitofrontal cortex in response to viewing high-calorie food pictures (high-calorie food vs. nonfood). (D) Activation of the visual cortex in response to viewing food pictures (food vs. nonfood). The color bar indicates the T value of the functional activity in each voxel. The blood oxygen level-dependent signal intensity (effect size) is presented as the mean and the standard error of the mean. The cluster level threshold was set to 10 voxels with an uncorrected P<0.001. x, y, and z indicate the x-axis (sagittal plane), y-axis (coronal plane), and z-axis (transverse plane) used in magnetic resonance imaging.

**Fig. 3** Alteration in the responses to visual food cues in the brain in lean and obese individuals with type 2 diabetes mellitus (T2DM) after the administration of lixisenatide. The color bar indicates the T value of the functional activity in a voxel. The cluster level threshold was set to 10 voxels with an uncorrected P<0.001. x, y, and z indicate the x-axis (sagittal plane), y-axis (coronal plane), and z-axis (transverse plane) used in magnetic resonance imaging.

**Fig. 4** Alteration in brain responses to visual food cues in 17 of 29 individuals (eight lean and nine obese individuals) with type 2 diabetes mellitus (T2DM) who had decreased caloric intake after the administration of lixisenatide. (A) Activation of the posterior cingulate and medial frontal cortex in response to viewing high-calorie food pictures (high-calorie food vs. low-calorie food). (B) Activation of the hypothalamus, temporal lobe, and orbitofrontal cortex in response to viewing food pictures (food vs. low-calorie food). The color bar indicates the T value of the functional activity in a voxel. The cluster level threshold was set to 10 voxels with an uncorrected P<0.001. x, y, and z indicate the x-axis (sagittal plane), y-axis (coronal plane), and z-axis (transverse plane) used in magnetic resonance imaging.

그림 출처: PubMed Central 공개 논문 (PMC7188972)

Conflict of interest statement

No potential conflict of interest relevant to this article was reported.

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