The Consistency in Macronutrient Oxidation and the Role for Epinephrine in the Response to Fasting and Overfeeding

Abstract

Context: In humans, dietary vs intraindividual determinants of macronutrient oxidation preference and the role of the sympathetic nervous system (SNS) during short-term overfeeding and fasting are unclear.

Objective: To understand the influence on metabolic changes of diet and SNS during 24 hours of overfeeding.

Design, setting, participants, and interventions: While residing on a clinical research unit, 64 participants with normal glucose regulation were assessed during energy balance, fasting, and four 24-hour overfeeding diets, given in random order. The overfeeding diets contained 200% of energy requirements and varied macronutrient proportions: (1) standard (50% carbohydrate, 20% protein, and 30% fat); (2) 75% carbohydrate; (3) 60% fat; and (4) 3% protein.

Main outcome measures: Twenty-four-hour energy expenditure (EE) and macronutrient oxidation rates were measured in an indirect calorimeter during the dietary interventions, with concomitant measurement of urinary catecholamines and free cortisol.

Results: EE decreased with fasting (-7.7% ± 4.8%; P < 0.0001) and increased with overfeeding. The smallest increase occurred during consumption of the diet with 3% protein (2.7% ± 4.5%; P = 0.001) and the greatest during the diet with 75% carbohydrate (13.8 ± 5.7%; P < 0.0001). Approximately 60% of macronutrient oxidation was determined by diet and 20% by intrinsic factors (P < 0.0001). Only urinary epinephrine differed between fasting and overfeeding diets (Δ = 2.25 ± 2.9 µg/24h; P < 0.0001). During fasting, higher urinary epinephrine concentrations correlated with smaller reductions in EE (ρ = 0.34; P = 0.01).

Conclusions: Independent from dietary macronutrient proportions, there is a strong individual contribution to fuel preference that remains consistent across diets. Higher urinary epinephrine levels may reflect the importance of epinephrine in maintaining EE during fasting.

Trial registration: ClinicalTrials.gov NCT00523627.

Figure 1.

Flow diagram of volunteer inclusion and participation in study.

Figure 2.

Graphic of (A) EE and (B) related RQ of each different dietary intervention and of (C) mean carbohydrate (CHO) and lipid intake and oxidation. (A) EE/min and (B) RQ data series over 23.25 hours during all dietary interventions and compared with EB (shown in dark blue). The EE/min and temporal RQ during overfeeding (OF) are shown with the standard OF diet (n = 64; 50% CHO, 30% fat, and 20% protein) in black; the high-CHO OF diet (n = 63; 75% CHO, 5% fat, and 20% protein) in fuchsia; the high-fat OF diet (n = 63; 20% CHO, 60% fat, and 20% protein) in purple; and the low-protein OF diet (n = 62; 51% CHO, 46% fat, and 3% protein) in green. The EE/min and RQ during fasting (n = 64) are shown in light blue. The 0:00 time period indicates entry into the respiratory chamber (∼1 hour after consuming breakfast); lunch was given at the 3-hour mark, dinner at the 8-hour mark, and a snack at the 11-hour mark. Participants were asked to be in bed from the 15-hour mark to at least the 21-hour mark in the chamber, and to limit unnecessary activity throughout the 24-hour period. All trajectories were different from all other trajectories (P < 0.0001). (C) Graphic representation of mean for CHO intake in black, lipid intake in white, carbox in horizontal stripes, and lipox in dots during the different diets. Overall, despite the increase in MO following the respective increase in the amount of each specific macronutrient ingested, the amount of energy burned was less than energy ingested. Note that for high-fat OF, on average, all of the CHO given was oxidized.

Figure 3.

Pie-chart representing the contribution of diet in white/black dots, intraindividual factors on (A) carbox and (B) lipox rates in black, and undefined physiological factors in white. Intraindividual correlation between (C) carbox and (D) lipox during the high-fat (60%) and high-carbohydrate (75%; high-CHO) diets and between (E) carbox and (F) lipox during the 75% CHO and standard overfeeding (OF) diets. All correlations were adjusted for age, sex, FM, and FFM. Correlation between (G) 24-hour urinary epinephrine concentration and percent EE change during fasting, indicating possible role of epinephrine in thrifty vs spendthrift phenotypes. (H) Correlations between average 24-hour urinary epinephrine concentration during all diets and percent body fat.