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

Cirulli, ET, Guo, L, Swisher, CL, Shah, N, Huang, L, Napier, LA, Kirkness, EF, Spector, TD, Caskey, CT, Thorens, B, Venter, JC and Telenti, A 2019 , 'Profound perturbation of the metabolome in obesity is associated with health risk' , Cell Metabolism, vol. 29, no. 2 , 488–500 , doi: 10.1016/j.cmet.2018.09.022.

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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.

Item Type: Article
Authors/Creators:Cirulli, ET and Guo, L and Swisher, CL and Shah, N and Huang, L and Napier, LA and Kirkness, EF and Spector, TD and Caskey, CT and Thorens, B and Venter, JC and Telenti, A
Keywords: diabetes, obesity, insulin resisatnce, liver
Journal or Publication Title: Cell Metabolism
Publisher: Cell Press
ISSN: 1550-4131
DOI / ID Number: 10.1016/j.cmet.2018.09.022
Copyright Information:

Copyright 2018 The Authors

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