The counterbalancing effects of energy expenditure on body weight regulation: Orexigenic versus energy-consuming mechanisms

Abstract

Objective: Weight change is a dynamic function of whole-body energy balance resulting from the interplay between energy intake and energy expenditure (EE). Recent reports have provided evidence for the existence of a causal effect of EE on energy intake, suggesting that increased EE may drive overeating, thereby promoting future weight gain. This study investigated the relationships between ad libitum energy intake and 24-hour EE (24-h EE) in sedentary conditions versus long-term, free-living weight change using a mediation analysis framework.

Methods: Native American individuals (n = 61, body fat by dual-energy x-ray absorptiometry: 39.7% [SD 9.5%]) were admitted to the clinical inpatient unit and had baseline measurements as follows: 1) 24-h EE accurately measured in a whole-room indirect calorimeter during energy balance and weight stability; and 2) ad libitum energy intake objectively assessed for 3 days using computerized vending machines. Free-living weight change was assessed after a median follow-up time of 1.7 years (interquartile range: 1.2-2.9).

Results: The total effect of 24-h EE on weight change (-0.23 kg per 100-kcal/d difference in EE at baseline) could be partitioned into the following two independent and counterbalanced effects: higher EE protective against weight gain (-0.46 kg per 100-kcal/d difference in EE at baseline) and an orexigenic effect promoting overeating, thereby favoring weight gain (+0.23 kg per 100-kcal/d difference in EE at baseline).

Conclusions: The overall impact of EE on body weight regulation should be evaluated by also considering its collateral effect on energy intake. Any weight loss intervention aimed to induce energy deficits by increasing EE should take into account any potential orexigenic effects that promote compensatory overeating, thereby limiting the efficacy of these obesity therapies.

FIGURE 1

Dissecting the dual effects of 24‐h EE on weight change by considering its influence on ad libitum energy intake. Mediation analysis was performed using the causal model framework described previously (18) to partition the total effect of 24‐h EE (independent variable) on weight change (dependent variable, median follow‐up time: 1.7 years) into the direct, “energy‐consuming” effect of 24‐h EE per se and the indirect, “orexigenic” effect via ad libitum energy intake (mediator). At the baseline inpatient visit, participants had accurate measurements of 24‐h EE in a whole‐room indirect calorimeter during eucaloric conditions and objective assessments of ad libitum energy intake over 3 days using a highly reproducible computerized vending machine paradigm. Following discharge, all individuals had a follow‐up outpatient visit when body weight was recorded. EE, energy expenditure; 24‐h EE, 24‐hour EE

FIGURE 2

Counterbalancing effects of 24‐h EE on weight change. Effects are shown as mean (SE). The total effect of 24‐h EE on weight change (−0.23 kg per 100‐kcal/d difference in 24‐h EE) is the net sum of the direct, “energy‐consuming” effect of 24‐h EE per se (−0.46 kg per 100 kcal/d) and the indirect, “orexigenic” effect via ad libitum energy intake (+0.23 kg per 100 kcal/d). The indirect effect of 24‐h EE on weight change was calculated as the product of the two path coefficients between 24‐h EE → ad libitum energy intake and ad libitum energy intake → weight change, as shown in the mediation analysis scheme of Figure 1, in which the following apply: 1) the path coefficient between 24‐h EE and ad libitum energy intake was calculated as the β coefficient estimate of 24‐h EE from the respective linear regression model; and 2) the path coefficient between ad libitum energy intake and weight change was calculated as the β coefficient estimate of ad libitum energy intake from the multivariate regression model including 24‐h EE as covariate. EE, energy expenditure; 24‐h EE, 24‐hour EE