Impaired metabolic flexibility to fasting is associated with increased ad libitum energy intake in healthy adults.

OBJECTIVE: We investigated how changes in 24-h respiratory exchange ratio (RER) and substrate oxidation during fasting versus an energy balance condition influence subsequent ad libitum food intake. METHODS: Forty-four healthy, weight-stable volunteers (30 male and 14 female; mean [SD], age 39.3 [11.0] years; BMI 31.7 [8.3] kg/m2) underwent 24-h energy expenditure measurements in a respiratory chamber during energy balance (50% carbohydrate, 30% fat, and 20% protein) and 24-h fasting. Immediately after each chamber stay, participants were allowed 24-h ad libitum food intake from computerized vending machines. RESULTS: Twenty-four-hour RER decreased by 9.4% (95% CI: -10.4% to -8.5%; p < 0.0001) during fasting compared to energy balance, reflecting a decrease in carbohydrate oxidation (mean [SD], -2.6 [0.8] MJ/day; p < 0.0001) and an increase in lipid oxidation (2.3 [0.9] MJ/day; p < 0.0001). Changes in 24-h RER and carbohydrate oxidation in response to fasting were correlated with the subsequent energy intake such that smaller decreases in fasting 24-h RER and carbohydrate oxidation, but not lipid oxidation, were associated with greater energy intake after fasting (r = 0.31, p = 0.04; r = 0.40, p = 0.007; and r = -0.27, p = 0.07, respectively). CONCLUSIONS: Impaired metabolic flexibility to fasting, reflected by an inability to transition away from carbohydrate oxidation, is linked with increased energy intake.

Closed-loop control of air supply to whole-room indirect calorimeters to improve accuracy and standardize measurements during 24-hour dynamic metabolic studies.

OBJECTIVE: The aim of this study was to test proportional-integral-derivative (PID) control of air inflow rate in a whole-room indirect calorimeter to improve accuracy in measuring oxygen (O2 ) consumption ( V ̇ O 2 ) and carbon dioxide (CO2 ) production ( V ̇ CO 2 ). METHODS: A precision gas blender infused nitrogen (N2 ) and CO2 into the calorimeter over 24 hours based on static and dynamic infusion profiles mimicking V ̇ O 2 and V ̇ CO 2 patterns during resting and non-resting conditions. Constant (60 L/min) versus time-variant flow set by a PID controller based on the CO2 concentration was compared based on errors between measured versus expected values for V ̇ O 2 , V ̇ CO 2 , respiratory exchange ratio, and metabolic rate. RESULTS: Compared with constant inflow, the PID controller allowed both a faster rise time and long-term maintenance of a stable CO2 concentration inside the calorimeter, resulting in more accurate V ̇ CO 2 estimates (mean hourly error, PID: -0.9%, 60 L/min = -2.3%, p < 0.05) during static infusions. During dynamic infusions mimicking exercise sessions, the PID controller achieved smaller errors for V ̇ CO 2 (mean: -0.6% vs. -2.7%, p = 0.02) and respiratory exchange ratio (mean: 0.5% vs. -3.1%, p = 0.02) compared with constant inflow conditions, with similar V ̇ O 2 (p = 0.97) and metabolic rate (p = 0.76) errors. CONCLUSIONS: PID control in a whole-room indirect calorimeter system leads to more accurate measurements of substrate oxidation during dynamic metabolic studies.

Metabolic Responses to 24-Hour Fasting and Mild Cold Exposure in Overweight Individuals Are Correlated and Accompanied by Changes in FGF21 Concentration.

A greater decrease in 24-h energy expenditure (24 EE) during 24-h fasting defines a "thriftier" metabolic phenotype prone to weight gain during overfeeding and resistant to weight loss during caloric restriction. As the thermogenic response to mild cold exposure (COLD) may similarly characterize this human phenotype identified by acute fasting conditions, we analyzed changes in 24 EE and sleeping metabolic rate (SLEEP) in a whole-room indirect calorimeter during 24-h fasting at thermoneutrality (24°C) and during energy balance both at thermoneutrality (24°C) and mild cold (19°C) in 20 healthy volunteers (80% male; aged 36.6 ± 11.4 years; percentage body fat 34.8 ± 10.5%). Greater decrease in 24 EE during fasting (thriftier phenotype) was associated with less increase in 24 EE during COLD (i.e., less cold-induced thermogenesis). Greater decreases in plasma fibroblast growth factor 21 (FGF21) after 24-h fasting and after COLD were highly correlated and associated with greater decreases in SLEEP in both conditions. We conclude that the metabolic responses to short-term fasting and COLD are associated with and mediated by the liver-derived hormone FGF21. Thus, the 24 EE response to COLD further identifies the "thrifty" versus "spendthrift" phenotype, providing an additional setting to investigate the physiological mechanisms underlying the human metabolic phenotype and characterizing the individual susceptibility to weight change.