Lipid ratios representing SCD1, FADS1, and FADS2 activities as candidate biomarkers of early growth and adiposity
L. Olga,
J.A. van Diepen,
I. Bobeldijk-Pastorova,
G. Gross,
P.M. Prentice,
S.G. Snowden,
S. Furse,
T. Kooistra,
I.A. Hughes,
M.H. Schoemaker,
E.A.F. van Tol,
W. van Duyvenvoorde,
P.Y. Wielinga,
K.K. Ong,
D.B. Dunger,
R. Kleemann,
A. Koulman
Affiliations
L. Olga
Department of Paediatrics, University of Cambridge, Cambridge, UK
J.A. van Diepen
Mead Johnson Pediatric Nutrition Institute, Nijmegen, the Netherlands
I. Bobeldijk-Pastorova
Department of Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), Leiden, The Netherlands
G. Gross
Mead Johnson Pediatric Nutrition Institute, Nijmegen, the Netherlands
P.M. Prentice
Department of Paediatrics, University of Cambridge, Cambridge, UK
S.G. Snowden
Core Metabolomics and Lipidomics Laboratory, Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK
S. Furse
Core Metabolomics and Lipidomics Laboratory, Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK
T. Kooistra
Department of Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), Leiden, The Netherlands
I.A. Hughes
Department of Paediatrics, University of Cambridge, Cambridge, UK
M.H. Schoemaker
Mead Johnson Pediatric Nutrition Institute, Nijmegen, the Netherlands
E.A.F. van Tol
Mead Johnson Pediatric Nutrition Institute, Nijmegen, the Netherlands; Department of Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), Leiden, The Netherlands
W. van Duyvenvoorde
Department of Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), Leiden, The Netherlands
P.Y. Wielinga
Department of Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), Leiden, The Netherlands
K.K. Ong
Department of Paediatrics, University of Cambridge, Cambridge, UK; MRC Epidemiology Unit, Wellcome Trust-MRC Institute of Metabolic Science, NIHR Cambridge Comprehensive Biomedical Research Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, UK; Wellcome-MRC Institute of Metabolic Science-Metabolic Research Laboratories’ or (IMS-MRL), University of Cambridge, Cambridge, UK
D.B. Dunger
Department of Paediatrics, University of Cambridge, Cambridge, UK; Wellcome-MRC Institute of Metabolic Science-Metabolic Research Laboratories’ or (IMS-MRL), University of Cambridge, Cambridge, UK
R. Kleemann
Department of Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), Leiden, The Netherlands; Department of Vascular Surgery, Leiden University Medical Center, Leiden, The Netherlands
A. Koulman
Core Metabolomics and Lipidomics Laboratory, Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; MRC Epidemiology Unit, Wellcome Trust-MRC Institute of Metabolic Science, NIHR Cambridge Comprehensive Biomedical Research Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, UK; Wellcome-MRC Institute of Metabolic Science-Metabolic Research Laboratories’ or (IMS-MRL), University of Cambridge, Cambridge, UK; Corresponding author: Dr Albert Koulman, Scientific Director of the NIHR BRC Core Metabolomics and Lipidomics Laboratory, Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science-Metabolic Research Laboratories University of Cambridge School of Clinical Medicine Cambridge Biomedical Campus Cambridge CB2 0QQ United Kingdom. Telephone: +44 (0)1223 336792+44 (0)1223 336792+44 (0)1223 336792
Background: Altered lipid metabolism in early life has been associated with subsequent weight gain and predicting this could aid in obesity prevention and risk management. Here, a lipidomic approach was used to identify circulating markers for future obesity risk in translational murine models and validate in a human infant cohort. Methods: Lipidomics was performed on the plasma of APOE*3 Leiden, Ldlr-/-.Leiden, and the wild-type C57BL/6J mice to capture candidate biomarkers predicting subsequent obesity parameters after exposure to high-fat diet. The identified candidate biomarkers were mapped onto corresponding lipid metabolism pathways and were investigated in the Cambridge Baby Growth Study. Infants’ growth and adiposity were measured at 0-24 months. Capillary dried blood spots were sampled at 3 months for lipid profiling analysis. Findings: From the mouse models, cholesteryl esters were correlated with subsequent weight gain and other obesity parameters after HFD period (Spearman's r≥0.5, FDR p values <0.05) among APOE*3 Leiden and Ldlr-/-.Leiden mice, but not among the wild-type C57BL/6J. Pathway analysis showed that those identified cholesteryl esters were educts or products of desaturases activities: stearoyl-CoA desaturase-1 (SCD1) and fatty acid desaturase (FADS) 1 and 2. In the human cohort, lipid ratios affected by SCD1 at 3 months was inversely associated with 3-12 months weight gain (B±SE=-0.31±0.14, p=0.027), but positively with 12-24 months weight and adiposity gains (0.17±0.07, p=0.02 and 0.17±0.07, 0.53±0.26, p=0.04, respectively). Lipid ratios affected by SCD1 and FADS2 were inversely associated with adiposity gain but positively with height gain between 3-12 months. Interpretation: From murine models to human setting, the ratios of circulating lipid species indicating key desaturase activities in lipid metabolism were associated with subsequent body size increase, providing a potential tool to predict early life weight gain.
