Modified sham feeding of foods with different macronutrient compositions differentially influences cephalic change of insulin, ghrelin, and NMR-based metabolomic profiles

• Modified sham feeding induced a macronutrient-specific cephalic change in insulin and ghrelin.
• Modified sham feeding resulted in a macronutrient-specific cephalic change in metabolomic profiles.
• Plasma glucose increased after modified sham feeding but this was not macronutrient-specific.

Little is known about the effect of the macronutrient composition of foods on cephalic phase response of gastrointestinal hormones. In addition, the metabolomics of cephalic phase response has not been studied before. The objective of the present study was to assess cephalic phase endocrinological and metabolomic responses following modified sham feeding (MSF) of foods with different macronutrient compositions. Ten healthy males attended four separate test sessions after overnight fasting, for a 3-min MSF of water, high-fat, high-carbohydrate or high-protein food, respectively, in a randomized order. Blood samples were collected at baseline and at regular time points for 10 min following the completion of MSF and assayed for plasma glucose, insulin, ghrelin and glucose-dependent insulinotropic peptide. 1H nuclear magnetic resonance was used to acquire metabolomic profiles of the plasma samples. Plasma glucose increased after MSF of all test foods, but there were no differences due to the macronutrient composition of the test foods. MSF of the high-carbohydrate food elicited significantly higher insulin, and the high-protein food resulted in higher ghrelin compared to other test sessions. No significant change in glucose-dependent insulinotropic peptide was found. Analysis of plasma metabolomic profiles revealed concentrations of lipids were lower after MSF while plasma glucose increased after MSF. There was also a macronutrient-dependent change in certain amino acids. In conclusion, short-term oral exposure to foods with different macronutrient compositions can induce a macronutrient-specific cephalic change in insulin and ghrelin, as well as metabolomic profiles.