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

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.

Aberrant Brain Functional Connectivity Strength and Effective Connectivity in Patients with Type 2 Diabetes Mellitus

“…Hypertriglyceridemia is a common symptom of diabetes which was also found in T2DM patients in our study; the correlation results indicate the important roles of the fusiform and lingual gyrus in the neural pathways of lipid metabolism. In addition, a positive correlation was found between the 2 h postprandial insulin and the decreased inflow from the left fusiform gyrus to the left lingual gyrus, which is interpretable as previous research reported that the plasma insulin level is associated with cue-induced appetite at both neural and behavioral levels, which can affect activation of the fusiform gyrus in response to visual processing [ 30 , 31 ]. Furthermore, 2hPG was positively correlated with the increased inflow from the left fusiform gyrus to the right MFG.…”

Neural Correlates of Anti-appetite Medications: An fMRI Meta-analysis

“…The number of participants per study ranged from 8 to 48. Five studies recruited an equal ratio of males and females, whereas six studies recruited females only, and four studies recruited males only (Table 1 ) [ 16 - 39 ]. Twelve studies recruited healthy subjects only, and numerous studies recruiting subjects with overweight/obesity and type 2 diabetes.…”

Fasting oxyntomodulin, glicentin, and gastric inhibitory polypeptide levels are associated with activation of reward‐ and attention‐related brain centres in response to visual food cues in adults with obesity: A cross‐sectional functional MRI study

“…Moreover, a negative association, weaker compared to reward areas but still significant, was observed both for oxyntomodulin and glicentin with the activation of the hypothalamus. Greater activation of the hypothalamus has recently been reported in people with obesity compared to lean individuals with T2DM 15 . Additionally, hypothalamic activation was reduced after treatment with the GLP‐1RA lixisenatide among individuals with obesity who had decreased their caloric intake 15 .…”

“…Greater activation of the hypothalamus has recently been reported in people with obesity compared to lean individuals with T2DM. 15 Additionally, hypothalamic activation was reduced after treatment with the GLP-1RA lixisenatide among individuals with obesity who had decreased their caloric intake. 15 However, given that the hypothalamus hosts both orexigenic and anorexigenic pathways, it is difficult to assess the net impact on appetite and energy intake of the negative association of hormonal levels with hypothalamic activation that we observed in the present study.…”

“…15 Additionally, hypothalamic activation was reduced after treatment with the GLP-1RA lixisenatide among individuals with obesity who had decreased their caloric intake. 15 However, given that the hypothalamus hosts both orexigenic and anorexigenic pathways, it is difficult to assess the net impact on appetite and energy intake of the negative association of hormonal levels with hypothalamic activation that we observed in the present study. Finally, GIP is secreted by K cells located in the mucosa F I G U R E 1 Results of whole-brain regression with A, gastric inhibitory polypeptide, B, oxyntomodulin and C, glicentin levels in the fasting state while viewing highly desirable compared to less desirable food images.…”