Habitual physical activity and plasma metabolomic patterns distinguish individuals with low vs. high weight loss during controlled energy restriction

Abstract

Background: Total weight loss induced by energy restriction is highly variable even under tightly controlled conditions. Identifying weight-loss discriminants would provide a valuable weight management tool and insights into body weight regulation.

Objective: This study characterized responsiveness to energy restriction in adults from variables including the plasma metabolome, endocrine and inflammatory markers, clinical indices, body composition, diet, and physical activity.

Methods: Data were derived from a controlled feeding trial investigating the effect of 3-4 dairy product servings in an energy-restricted diet (2092 kJ/d reduction) over 12 wk. Partial least squares regression was used to identify weight-loss discriminants in 67 overweight and obese adults. Linear mixed models were developed to identify discriminant variable differences in high- vs. low-weight-loss responders.

Results: Both pre- and postintervention variables (n = 127) were identified as weight-loss discriminants (root mean squared error of prediction = 1.85 kg; Q(2) = 0.43). Compared with low-responders (LR), high-responders (HR) had greater decreases in body weight (LR: 2.7 ± 1.6 kg; HR: 9.4 ± 1.8 kg, P < 0.01), BMI (in kg/m(2); LR: 1.0 ± 0.6; HR: 3.3 ± 0.5, P < 0.01), and total fat (LR: 2.2 ± 1.1 kg; HR: 8.0 ± 2.1 kg, P < 0.01). Significant group effects unaffected by the intervention were determined for the respiratory exchange ratio (LR: 0.86 ± 0.05; HR: 0.82 ± 0.03, P < 0.01), moderate physical activity (LR: 127 ± 52 min; HR: 167 ± 68 min, P = 0.02), sedentary activity (LR: 1090 ± 99 min; HR: 1017 ± 110 min, P = 0.02), and plasma stearate [LR: 102,000 ± 21,000 quantifier ion peak height (QIPH); HR: 116,000 ± 24,000 QIPH, P = 0.01].

Conclusions: Overweight and obese individuals highly responsive to energy restriction had accelerated reductions in adiposity, likely supported in part by higher lipid mobilization and combustion. A novel observation was that person-to-person differences in habitual physical activity and magnitude of weight loss were accompanied by unique blood metabolite signatures. This trial was registered at clinicaltrials.gov as NCT00858312.

Keywords: body composition; branched-chain amino acids; calorie restriction; metabolomics; obesity; physical activity; respiratory exchange ratio; statistical modeling; weight loss.

© 2015 American Society for Nutrition.

Figures

FIGURE 1

Schematic of multivariate statistical modeling approach of weight loss in overweight and obese subjects consuming an energy deficit of 2092 kJ/d (500 kcal/d) for 12 wk. PLSR, partial least squares regression; RMSEP, root mean square error of prediction; VIP, variable importance in projection.

FIGURE 2

Distribution histogram (A) and Q-Q plot (B) of total weight loss in overweight and obese subjects (n = 67) after consuming an energy deficit of 2092 kJ/d (500 kcal/d) for 12 wk. Q, quantile.

FIGURE 3

Pre- and postintervention changes in selected clinical, adiposity, and endocrine indices including total fat mass (A), body fat (B), android fat (C), gynoid fat (D), total:HDL cholesterol ratio (E), and plasma leptin (F) in high- and low-weight–loss responders. Variables presented in the figure had a significant interaction term in linear mixed model analyses. High-responder (circles) and low-responder (triangles) represent high- and low-weight–loss tertiles, respectively. Serum cholesterol, HDL cholesterol, and leptin were measured after an overnight fast. Values are means ± SEMs, n = 22 for both groups. Post-, postintervention; Pre-, preintervention.

FIGURE 4

Pre- and postintervention changes in selected plasma metabolites, including citric acid (A), succinic acid (B), dodecanol (C), arachidic acid (D), threonic acid (E), and dihydro-3-coumaric acid (F) in high- and low-weight–loss responders. Metabolites presented in the figure had a significant interaction term in linear mixed model analyses. High-responder (circles) and low-responder (triangles) represent high- and low-weight–loss tertiles, respectively. Plasma metabolites were measured after an overnight fast. Values are means ± SEMs, n = 22 for both groups. Post-, postintervention; Pre-, preintervention; QIPH, quantifier ion peak height.

FIGURE 5

Spearman correlation matrix of variables associated with weight-loss responsiveness in overweight and obese men and women (n = 67) consuming an energy deficit of 2092 kJ/d (500 kcal/d) for 12 wk. Variables were selected by partial least squares regression as discriminant of weight loss and found to be significantly different between high- and low-responders in linear mixed model analyses. High-responder and low-responder represent high- and low-weight–loss tertiles (n = 22 for both groups), respectively. Direction or color of ellipses represent positive or negative correlation, respectively. Darker color and thinner ellipses represent strength (Spearman’s ρ) of correlations. Only significant correlations at α = 0.05 are displayed. BB, BinBase identification numbers; QIPH, quantifier ion peak height.