Abstract
Weight loss (WL) induced by energy restriction is highly variable even in controlled clinical trials. An integrative analysis of the plasma metabolome coupled to traditional clinical variables may reveal a WL “responder” phenotype. Therfore, we predicted WL in overweight and obese individuals on an energy‐restricted diet in a controlled feeding trial using the plasma metabolome in addition to clinical indices, body composition parameters, plasma endocrine and inflammatory markers, dietary parameters, and physical activity (PA) measurements. A total of 940 pre‐intervention (PrI) and post‐intervention (PoI) variables were assessed. Partial least squares regression accurately predicted weight loss along latent variable 1 (root mean error of prediction (RMSEP) = 1.81 kgs; Q2 = 0.43) and revealed that PrI light and moderate PA were associated with high weight loss, whereas PoI sedentary PA and 2‐ketoisocaproic acid were associated with low weight loss. Network correlation analysis revealed a direct connection between lower PrI respiratory quotient, higher PoI 3‐hydroxybutanoic acid and higher PoI citric acid (P < 0.00001) in high weight losers. Our results suggest that habitual light‐to‐moderate PA are accompanied by distinct blood amino acid and lipid metabolic signatures and correlated with WL in overweight and obese individuals under controlled conditions.Grant Funding Source: Supported by: Nat. Dairy Council; CA Dairy Res. Council; USDA; NCRR (UL1 RR024146); NIH (U24 DK097154)
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