The association between gut hormones and diet‐induced metabolic flexibility in metabolically healthy adults

Abstract Objective This study investigated whether interindividual variance in diet‐induced metabolic flexibility is explained by differences in gut hormone concentrations. Methods A total of 69 healthy volunteers with normal glucose regulation underwent 24‐hour assessments of respiratory quotient (RQ) in a whole‐room indirect calorimeter during eucaloric feeding (EBL; 50% carbohydrate, 30% fat) and then, in a crossover design, during 24‐hour fasting and three normal‐protein (20%) overfeeding diets (200% energy requirements). Metabolic flexibility was defined as the change in 24‐hour RQ from EBL during standard (50% carbohydrate), high‐fat (60%), and high‐carbohydrate (75%) overfeeding diets. Plasma concentrations of glucagon‐like peptide‐1 (GLP‐1) and peptide YY (PYY) after an overnight fast were measured prior to and after each diet. Results Compared with EBL, on average, 24‐hour RQ decreased by ~4% during high‐fat overfeeding, whereas it increased by ~4% during standard overfeeding and by ~9% during high‐carbohydrate overfeeding. During high‐carbohydrate overfeeding, but not during any other overfeeding diet or fasting, increased GLP‐1 concentration was associated with increased RQ ( r = 0.44, p < 0.001), higher/lower carbohydrate/lipid oxidation rates ( r = 0.34 and r = −0.51, both p < 0.01), respectively, and increased plasma insulin concentration ( r = 0.38, p = 0.02). Conclusions Increased GLP‐1 concentration following high‐carbohydrate overfeeding associated with a greater shift to carbohydrate oxidation, suggesting that GLP‐1 may be implicated in diet‐induced metabolic flexibility to carbohydrate overload.