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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.

SUBMITTER: Bae JH

PROVIDER: S-EPMC7188972 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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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.

Bae Jae Hyun JH Choi Hyung Jin HJ Cho Kang Ik Kevin KIK Kim Lee Kyung LK Kwon Jun Soo JS Cho Young Min YM

Diabetes & metabolism journal 20191104 2

<h4>Background</h4>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.<h4>Methods</h4>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, ...[more]

PMID: 31701698

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Project description:PurposeObesity is characterized by chronic inflammation that may contribute to insulin resistance and promote type 2 diabetes. We have investigated whether inflammatory responses to glycemic and insulinemic variations are altered in obese individuals.MethodsEight obese and eight lean individuals without diabetes had undergone hyperinsulinemic-euglycemic-hypoglycemic and hyperglycemic clamps in a previous study. Using Proximity Extension Assay, 92 inflammatory markers were analyzed from plasma samples at fasting, hyperinsulinemia-euglycemia, hypoglycemia and hyperglycemia.ResultsIn all participants, hyperinsulinemia, hypoglycemia and hyperglycemia led to reductions of 11, 19 and 62 out of the 70 fully evaluable biomarkers, respectively. FGF-21 increased during both hypoglycemia and hyperglycemia while IL-6 and IL-10 increased during hypoglycemia. In obese vs lean participants, Oncostatin-M, Caspase-8 and 4E-BP1 were more markedly suppressed during hypoglycemia, whereas VEGF-A was more markedly suppressed during hyperglycemia. BMI correlated inversely with changes of PD-L1 and CD40 during hyperinsulinemia, Oncostatin-M, TNFSF14, FGF-21 and 4EBP-1 during hypoglycemia and CCL23, VEGF-A and CDCP1 during hyperglycemia (Rho ≤ -0.50). HbA1c correlated positively with changes of MCP-2 and IL-15-RA during hyperinsulinemia (Rho ≥ 0.51) and inversely with changes of CXCL1, MMP-1 and Axin-1 during hypoglycemia (Rho ≤ -0.55). M-value correlated positively with changes of IL-12B and VEGF-A during hyperglycemia (Rho ≥ 0.51). Results above were significant (p < 0.05).ConclusionOverall, hyperinsulinemia, hypo- and hyperglycemia led to suppression of several inflammatory markers and this tended to be more marked in individuals with obesity, insulin resistance and dysglycemia. Thus, acute glycemic or insulinemic variations do not seem to potentiate possible inflammatory pathways in the development of insulin resistance and disturbed glucose metabolism.

Project description:BackgroundDiurnal variation of natriuretic peptide (NP) levels and its relationship with 24-h blood pressure (BP) rhythm has not been established. Obese individuals have a relative NP deficiency and disturbed BP rhythmicity.ObjectivesThis clinical trial evaluated the diurnal rhythmicity of NPs (B-type natriuretic peptide [BNP], mid-regional pro-atrial natriuretic peptide [MR-proANP], N-terminal pro-B-type natriuretic peptide [NT-proBNP]) and the relationship of NP rhythm with 24-h BP rhythm in healthy lean and obese individuals.MethodsOn the background of a standardized diet, healthy, normotensive, lean (body mass index 18.5 to 25 kg/m2) and obese (body mass index 30 to 45 kg/m2) individuals, age 18 to 40 years, underwent 24-h inpatient protocol involving ambulatory BP monitoring starting 24 h prior to the visit, controlled light intensity, and repeated blood draws for assessment of analytes. Cosinor analysis of normalized NP levels (normalized to 24-h mean value) was conducted to assess the diurnal NP rhythm and its relationship with systolic BP.ResultsAmong 52 participants screened, 40 participants (18 lean, 22 obese; 50% women; 65% Black) completed the study. The median range spread (percentage difference between the minimum and maximum values) over 24 h for MR-proANP, BNP, and NT-proBNP levels was 72.0% (interquartile range [IQR]: 50.9% to 119.6%), 75.5% (IQR: 50.7% to 106.8%), and 135.0% (IQR: 66.3% to 270.4%), respectively. A cosine wave-shaped 24-h oscillation of normalized NP levels (BNP, MR-proANP, and NT-proBNP) was noted both in lean and obese individuals (prhythmicity <0.05 for all). A larger phase difference between MR-proANP BP rhythm (-4.9 h vs. -0.7 h) and BNP BP rhythm (-3.3 h vs. -0.9 h) was seen in obese compared with lean individuals.ConclusionsThis human physiological trial elucidates evidence of diurnal NP rhythmicity and the presence of an NP-BP rhythm axis. There exists a misalignment of the NP-BP diurnal rhythm in the obese, which may contribute to the disturbed diurnal BP pattern observed among obese individuals. (The Diurnal Rhythm in Natriuretic Peptide Levels; NCT03834168).

Dataset Information

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.

Publications

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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