Metabolic adaptation is not observed after 8 weeks of overfeeding but energy expenditure variability is associated with weight recovery

Abstract

Background: A metabolic adaptation, defined as an increase in energy expenditure (EE) beyond what is expected with weight gain during overfeeding (OF), has been reported but also refuted. Much of the inconsistency stems from the difficulty in conducting large, well-controlled OF studies in humans.

Objectives: The primary aim of this study was to determine whether a metabolic adaptation to OF exists and if so, attenuates weight gain.

Methods: Thirty-five young adults consumed 40% above their baseline energy requirements for 8 wk, and sleeping metabolic rate (SMR) and 24-h sedentary energy expenditure (24h-EE) were measured before and after OF. Subjects were asked to return for a 6-mo post-OF follow-up visit to measure body weight, body composition, and physical activity.

Results: After adjusting for gains in fat-free mass and fat mass, SMR increased by 43 ± 123 kcal/d more than expected (P = 0.05) and 24h-EE by 23 ± 139 kcal/d (P = 0.34), indicating an overall lack of metabolic adaptation during OF despite a wide variability in the response. Among the 30 subjects who returned for the 6-mo follow-up visit, those who had a lower-than-predicted SMR (basal EE) retained more of the fat gained during OF. Likewise, subjects displaying a higher-than-predicted sedentary 24h-EE lost significantly more fat during the 6-mo follow-up.

Conclusions: Metabolic adaptation to OF was on average very small but variable between subjects, revealing "thrifty" or "spendthrift" metabolic phenotypes related to body weight loss 6 mo later. This trial was registered at clinicaltrials.gov as NCT01672632.

Keywords: dietary-induced thermogenesis; energy expenditure; luxuskonsumption; metabolic adaptation; overfeeding; respiratory chamber; sleeping metabolic rate; spendthrift phenotype; thrifty phenotype; weight gain.

FIGURE 1

“Residuals” in energy expenditure (EE) at baseline and after overfeeding (OF). “Residuals” are calculated as actual EE measurements minus predicted EE measurements, calculated using a previously published dataset (39). (A) Predicted sleeping metabolic rate (SMR, kcal/d) was calculated at baseline and post-OF in 34 adults (28 M, 6 F) as follows: Predicted SMR = 461 + (3.5 × FM) + (19.6 × FFM) − (70*race, where 1=African-American, 0=Caucasian), using measured values of fat mass (FM) and fat-free mass (FFM) at baseline and post-OF. After OF, mean SMR was significantly higher than predicted by 43 ± 123 kcal/d (*P = 0.05) by paired t test. (B) Predicted 24-h sedentary EE (24h-EE, kcal/d) was calculated at baseline and post-OF in all 35 adults (29 M, 6 F) as follows: Predicted 24h-EE = 546 + (5.2 × FM) + (26.2 × FFM) − (2.3 × age) − (96*race, where 1=African-American, 0=Caucasian), using measured values of FM and FFM at baseline and post-OF. Predicted 24h-EE after OF was not significantly different than measured 24h-EE (23 ± 139, P = 0.34) by paired t test, indicating the 24h-EE increased as expected for the increase in body mass.

FIGURE 2

In situ mitochondrial energetics of the vastus lateralis at rest before and after overfeeding. (A) ATP use measured by ³¹P-magnetic resonance spectroscopy did not change after overfeeding (OF) in 23 adults (19 M, 4 F) (6.2 ± 1.2 vs. 6.1 ± 1.3 µM ATP/s; P = 0.79). (B) There was a trend for oxygen use to decrease after OF in 21 adults (18 M, 3 F) (2.3 ± 0.6 vs. 2.0 ± 0.5 µM O₂/s; †P = 0.09) by paired t test. (C) Mitochondrial coupling efficiency (P/O ratio) did not change significantly after OF in 20 adults (18 M, 2 F) (1.35 ± 0.34 vs. 1.54 ± 0.50; P = 0.12) by paired t test.

FIGURE 3

Relation between deviations from predicted EE during overfeeding (OF) and body fat changes 6 mo later. (A) A lower-than-predicted sleeping metabolic rate (SMR) at baseline, suggestive of a more “thrifty” metabolic phenotype, was associated with greater retention of the fat mass gained during OF, after 6 mo of follow-up in 30 adults (25 M, 5 F) using Pearson correlation coefficients. (B) A greater-than-predicted sedentary 24-h energy expenditure (24h-EE) after OF, suggestive of a more “spendthrift” phenotype, was associated with significantly greater fat loss after 6 mo of follow-up in 30 adults (25 M, 5 F) using Pearson correlation coefficients. Shaded symbols represent the males and open symbols represent the females. FM, fat mass.