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

Background: Total weight loss induced by energy restriction is highly variable even under tightly controlled conditions. Identifying weight-loss discriminants would provide a valuableweightmanagement tool and insights into bodyweight 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; Q² = 0.43). Compared with low-responders (LR), high-responders (HR) had greater decreases in bodyweight (LR:2.7 ± 1.6 kg; HR:9.4 ± 1.8 kg, P < 0.01), BMI (in kg/m²; 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 6 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 andmagnitude of weight loss were accompanied by unique bloodmetabolite signatures. This trial was registered at clinicaltrials.gov as NCT00858312.