Food Intake-Related Brain and Metabolic Responses in Obesity

Brain Function, Feeding Behavior, Macronutrients, Metabolomics, Obesity

obesity, macronutrient, fMRI, Cross-over trial, Plasma metabolome, Satiety, Nutrient challenge

This study is a prospective, single-center, randomized, controlled, crossover intervention trial. A total of 60 participants, including 30 patients with obesity and 30 healthy controls, will be enrolled. Each participant will receive an isocaloric liquid meal challenge (glucose, fat, or protein) on three separate experimental days, with a washout period of at least 7 days between visits to eliminate carryover effects from the previous intervention. The primary objective is to investigate the association between brain functional patterns and plasma metabolic profiles following the ingestion of different macronutrients in patients with obesity, aiming to uncover potential neuro-metabolic imbalance features.

This study is a prospective, single-center, randomized, controlled, crossover intervention trial enrolling 60 participants, including 30 obese patients and 30 healthy control volunteers. Each participant will be randomly assigned to one of the six possible sequences of three macronutrient interventions (A: glucose, B: fat, C: protein)-namely ABC, ACB, BAC, BCA, CAB, or CBA-to ensure balanced allocation across intervention orders. Each participant will undergo one nutrient challenge on each of three separate experimental days, with at least a 7-day washout period between visits to minimize carryover effects from prior interventions. During the washout periods, participants are required to maintain stable habitual dietary patterns and avoid extreme diets, high-intensity exercise, irregular sleep schedules, and intake of additional nutritional supplements; adherence will be monitored via brief diet and activity logs. The intervention consists of isocaloric (200 kcal) and isovolumetric (300 mL) liquid meals, specifically formulated as follows: Glucose arm: 50 g glucose powder dissolved in water to a final volume of 300 mL; Fat arm: 100 mL intralipid emulsion diluted with water to a final volume of 300 mL; Protein arm: 54 g whey protein powder dissolved in water to a final volume of 300 mL. On each experimental day, participants must arrive in a fasting state. Prior to nutrient administration, they will complete clinical laboratory tests, body composition assessment, hepatic fat quantification, and eating behavior questionnaires. During and after the intervention, participants will provide dynamic postprandial satiety ratings, multi-timepoint blood and stool samples (for untargeted metabolomic analysis), and undergo functional magnetic resonance imaging (fMRI) within a predefined postprandial time window. Finally, neuroimaging metrics, peripheral metabolomic profiles, and subjective satiety scores will be integrated through multidimensional correlation analyses to explore the neuro-metabolic coupling responses to different macronutrient challenges in obesity, thereby providing theoretical insights and potential targets for precision nutrition interventions.

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