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

Brian D. Piccolo, Nancy L. Keim, Oliver Fiehn, Sean H. Adams, Marta D. Van Loan, John W. Newman

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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; Q<sup>2</sup> = 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/m<sup>2</sup>; 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.

Original languageEnglish (US)
Pages (from-to)681-690
Number of pages10
JournalJournal of Nutrition
Issue number4
StatePublished - 2015


  • Body composition
  • Branched-chain amino acids
  • Calorie restriction
  • Metabolomics
  • Obesity
  • Physical activity
  • Respiratory exchange ratio
  • Statistical modeling
  • Weight loss

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics


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