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

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.