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:	Refereed Article
Keywords:	diabetes, obesity, insulin resisatnce, liver
Research Division:	Biological Sciences
Research Group:	Biochemistry and cell biology
Research Field:	Cell metabolism
Objective Division:	Health
Objective Group:	Clinical health
Objective Field:	Clinical health not elsewhere classified
ID Code:	133384
Year Published:	2019
Web of Science® Times Cited:	139
Deposited By:	Health Sciences
Deposited On:	2019-06-24
Last Modified:	2019-07-23
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