Gut Hormone PYY Response to Overfeeding Is a Determinant of Metabolic Flexibility in Healthy Humans

Background: Metabolic flexibility is the ability to switch fuels for oxidation in response to changes in dietary macronutrient composition. Greater metabolic flexibility to fat is associated with less weight gain. The gut hormone PYY is associated with thermic effect of food and may play a role in fuel preference. We investigated whether changes in PYY with overfeeding diets are associated with changes in substrate oxdation. Methods: 69 healthy, weight-stable volunteers (53M/16F; Age 35.5 ± 10.5 yrs.; BMI 26.5 ± 4.2 kg/m2) with normal glucose regulation had 24hEE measurements in a whole-room indirect calorimeter during energy balance (EB: 50% carbohydrate, 20% protein), five overfeeding diets, and fasting in a crossover design. The overfeeding diets (200% of weight-maintaining energy requirements) included diets with 20% protein [50%-carbohydrate (BOF), 75%-carbohydrate (CNP), and 60%-fat (FNP)], %3 protein [Q carbohydrate (LPF) ] and 0 protein [& carbohydrate (HPF)]. Fasting plasma PYY concentrations were measured in the morning of and after each diet. Results: PYY increased following CNP, FNP, HPF and LPF overfeeding diets (Δ = +0.18 pg/ml, Δ = +0.13 pg/ml, Δ = +0.33 pg/ml, Δ = +0.27 pg/ml respectively, p values ≤ 0.01)and decreased following fasting and EB diets (Δ = −0.45 pg/ml, Δ = −0.25 pg/ml respectively, p values ≤ 0.01).Changes in PYY concentrations were not associated with changes in 24hEE measurements in any of the diet interventions. However, changes in PYY concentrations were positively associated with changes in adjusted 24hRQ and CARBOX rate after adjustments for age, sex and út in HPF, LPF and CNP diets (p values ≤ 0.04) and negatively associated with changes in LIPOX rate in the diets HPF and CNP (p values ≤ 0.03). Conclusions: Changes in PYY were associated with changes in substrate oxidation rates with overfeeding diets varying in macronutrient content. PYY may underpin the ability to alter fuel preference and may be a target to alter metabolic flexibility.