Models of energy homeostasis in response to maintenance of reduced body weight

Abstract

Objective: To test three proposed models for adaptive thermogenesis in compartments of energy expenditure following different degrees of weight loss. Specifically, (1) there is no adaptive thermogenesis [constant relationship of energy expenditure (EE) to metabolic mass]. (2) There is a fixed degree of adaptive thermogenesis once fat stores are below a "threshold." (3) The degree of adaptive thermogenesis is proportional to weight loss.

Methods: The relationship between weight loss and EE was examined in 17 inpatient subjects with stable weight and obesity studied at usual weight and again following a 10% and a 20% weight loss.

Results: Following initial weight loss (10%), resting (REE) and non-resting (NREE) EE were significantly below those predicted on the basis of the amount and composition of weight lost. Further reductions below predicted values of NREE but not REE occurred following an additional 10% weight loss. Changes in body weight, composition, and/or energy stores were significantly correlated with changes in EE.

Conclusions: All models are applicable to the decline in EE following weight loss. The disproportionate decline in REE is consistent with a threshold model (no change with further weight loss) while the disproportionate decline in NREE is largely reflective of the degree of weight loss.

Figure 1

Models of changes in EE during maintenance of a reduced body weight. A. Mechanical (solid line): In a mechanical model the reduction in EE following weight loss is directly proportional to the loss of energy stores (predominantly fat). B. Threshold (dashed line: In a threshold model, reduction of body energy stores below a threshold induces adaptive thermogenesis resulting in a decline in EE but there is no further increase in adaptive thermogenesis following more weight loss below the threshold. C. Spring loading (dotted line): In the stretching model the degree of adaptive thermogenesis is directly proportional to the amount of weight reduction being maintained.

Figure 2

Relationship between adaptive thermogenesis (residuals of TEE, REE, and NREE) and changes in body weight from Wt_initial in subjects at Wt_−10% and Wt_−20%. The regression equations are: $$\begin{array}{l}\text{TEE Residual}\left(\text{kcal}\right)=-201+10.5\ast \left[\text{Weight Loss}\left(\text{kg}\right)\right]\hfill \\ \mathrm{R}=0.35,\mathrm{p}=0.044\hfill \end{array}$$ $$\begin{array}{l}\text{REE Residual}\left(\text{kcal}\right)=-273–4.6\ast \left[\text{Weight Loss}\left(\text{kg}\right)\right]\hfill \\ \mathrm{R}=-0.19,\text{N.S}.\hfill \end{array}$$ $$\begin{array}{l}\text{NREE Residual}\left(\text{kcal}\right)=91+16.7\ast \left[\text{Weight Loss}\left(\text{kg}\right)\right]\hfill \\ \mathrm{R}=0.50,\mathrm{p}=0.003\hfill \end{array}$$

Figure 3

Schematic of study protocols and time range for each protocol phase for 17 subjects with obesity studied at Wt_initial, Wt_−10%, and Wt_−20% (Figure 3A), 50 subjects (20 never-obese, 30 obese) studied only at Wt_initial and Wt_−10% (Figure 3B), and 12 subjects (8 never-obese, 4 obese) studied at Wt_initial,Wt_+10%, and Wt_−10% (Figure 3C). There was no subject overlap between groups and subject characteristics are presented in Table 3. All subjects underwent the same protocols during each period of weight stability. Analyses of these additional data were performed to examine the effects of population size and diversity and weight gain versus loss on the relationship of changes in EE to changes in body mass and composition. *Weight gain was accomplished by overfeeding subjects solid food with a daily intake of 5000–7000 kcal/day until they had gained 10% of Wt_initial at which time they were stabilized on the liquid formula diet. ^† Weight loss was accomplished by underfeeding subjects 800 kcal/day of the liquid formula diet. Subjects with obesity suspended weight loss for 6–8 weeks when they had returned to their initial weight and were studied at that weight before reducing to Wt_−10%.

Figure 4

Relationship of adaptive thermogenesis (residuals of 24 hour EE (TEE)) at Wt_−10% and Wt_−20% in 17 subjects. The regression equation is: $$\text{TEE residual after additional weight loss}\left(\text{kcal}\right)=0.45\ast \text{[TEE residual after initial weight loss}(\text{kcal})]-55.2,\mathrm{R}=0.52,\mathrm{p}=0.019$$

Figure 5

A. Partitioning of absolute changes (4A) and percentage of the total decline (4B) in EE during the 1^st 10% weight loss (Wt_−10%−Wt_initial) and 2^nd 10% weight loss (Wt_−20%−Wt_−10%) plateaus attributable to each model. The mechanical effect is the mean number of calories predicted based on the regression equation relating EE to body composition (TEE and REE) or weight (NREE) at Wt_initial applied to both weight-reduced states. The threshold effect is whatever residual decline in EE occurs following the first 10% of weight loss but, by definition, does not increase once subjects have lost weight to a point below that threshold and cannot be attributed to the spring effect. The spring effect is whatever additional decline in EE residuals occurs between 10% and 20% weight loss (since the threshold model would predict no further decline in residuals after the first 10% weight reduction. As shown in Table 1, there is substantial inter-individual variation in these data.

Figure 5

A. Partitioning of absolute changes (4A) and percentage of the total decline (4B) in EE during the 1^st 10% weight loss (Wt_−10%−Wt_initial) and 2^nd 10% weight loss (Wt_−20%−Wt_−10%) plateaus attributable to each model. The mechanical effect is the mean number of calories predicted based on the regression equation relating EE to body composition (TEE and REE) or weight (NREE) at Wt_initial applied to both weight-reduced states. The threshold effect is whatever residual decline in EE occurs following the first 10% of weight loss but, by definition, does not increase once subjects have lost weight to a point below that threshold and cannot be attributed to the spring effect. The spring effect is whatever additional decline in EE residuals occurs between 10% and 20% weight loss (since the threshold model would predict no further decline in residuals after the first 10% weight reduction. As shown in Table 1, there is substantial inter-individual variation in these data.