Abstract

Body energy homeostasis is largely regulated by the interactions between appetite-related brain regions and gut hormones. We hypothesized that the sensitivity of appetite-related brain regions [eg, hypothalamus, insula, thalamus, parahippocampal/hippocampal cortex, caudate, putamen, amygdala, and orbitofrontal cortex (OFC)] varies for each macronutrient, and the differential sensitivity is associated with gut hormone concentrations in humans. Brain activation responses to ingested fat, glucose, protein, and water in the above-mentioned 8 brain regions of 14 healthy men were investigated by using functional magnetic resonance imaging. Fasting and postprandial plasma glucose, insulin, ghrelin, cholecystokinin (CCK), and glucagon-like peptide 1 (GLP-1) concentrations were measured. The relation of the blood oxygen level-dependent (BOLD) signal with plasma glucose and hormone concentrations was assessed by using Pearson's correlation analysis. Ingested macronutrients similarly reduced the BOLD signal in the middle insula, thalamus, parahippocampal cortex, caudate, and lateral OFC. Protein ingestion reduced the BOLD signal in the amygdala more effectively than did fat and glucose ingestion. BOLD signal changes were positively correlated with circulating ghrelin concentrations and were negatively correlated with circulating insulin, CCK, and GLP-1 concentrations. The findings indicate variations in the correlation between brain activation and plasma hormone concentrations after ingestion of different macronutrients. The middle insula, thalamus, parahippocampal cortex, caudate, and lateral OFC, but not the amygdala, have similar sensitivities to isocaloric and isovolumetric macronutrient solutions. Differential correlations exist between BOLD signal changes in activated brain regions and postprandial changes in plasma concentrations of different gut hormones in response to the ingestion of different macronutrients. This trial was registered at chictr.org as ChiCTR-TRC-12001945.

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