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

Obesity (Silver Spring). 2023 Jan;31(1):139-149. doi: 10.1002/oby.23584. Epub 2022 Dec 5.


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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carbohydrates
  • Diet
  • Energy Metabolism / physiology
  • Fasting* / physiology
  • Gastrointestinal Hormones*
  • Glucagon-Like Peptide 1
  • Humans
  • Insulin


  • Carbohydrates
  • Gastrointestinal Hormones
  • Glucagon-Like Peptide 1
  • Insulin