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

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 similar to 4% during high-fat overfeeding, whereas it increased by similar to 4% during standard overfeeding and by similar to 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.

Automated summary

This study investigated the relationship between interindividual variance in diet-induced metabolic flexibility and differences in gut hormone concentrations. The findings suggest that increased GLP-1 concentration following high-carbohydrate overfeeding is associated with a greater shift to carbohydrate oxidation.