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Profound perturbation of the metabolome in obesity is associated with health risk

journal contribution
posted on 2023-05-20, 04:49 authored by Cirulli, ET, Guo, L, Swisher, CL, Shah, N, Huang, L, Napier, LA, Kirkness, EF, Spector, TD, Caskey, CT, Thorens, B, Venter, JC, Telenti, A
Obesity is a heterogeneous phenotype that is crudely measured by body mass index (BMI). There is a need for a more precise yet portable method of phenotyping and categorizing risk in large numbers of people with obesity to advance clinical care and drug development. Here, we used non-targeted metabolomics and whole-genome sequencing to identify metabolic and genetic signatures of obesity. We find that obesity results in profound perturbation of the metabolome; nearly a third of the assayed metabolites associated with changes in BMI. A metabolome signature identifies the healthy obese and lean individuals with abnormal metabolomes - these groups differ in health outcomes and underlying genetic risk. Specifically, an abnormal metabolome associated with a 2- to 5-fold increase in cardiovascular events when comparing individuals who were matched for BMI but had opposing metabolome signatures. Because metabolome profiling identifies clinically meaningful heterogeneity in obesity, this approach could help select patients for clinical trials.

History

Publication title

Cell Metabolism

Volume

29

Pagination

488-500

ISSN

1550-4131

Publisher

Cell Press

Place of publication

United States

Rights statement

Copyright 2018 The Authors

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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