Urinary metabolic signatures of human adiposity

Obesity is a major public health problem worldwide. We used 24-hour urinary metabolic profiling by proton (1H) nuclear magnetic resonance (NMR) spectroscopy and ion exchange chromatography to characterize the metabolic signatures
of adiposity in the U.S. (n = 1880) and UK (n
= 444) cohorts of the INTERMAP (International Study of Macro- and
Micronutrients and Blood Pressure) epidemiologic study.
Metabolic profiling of urine samples collected
over two 24-hour time periods 3 weeks apart showed reproducible patterns
metabolite excretion associated with adiposity.
Exploratory analysis of the urinary metabolome using 1H NMR spectroscopy of the U.S. samples identified 29 molecular species, clustered in interconnecting metabolic pathways, that
were significantly associated (P = 1.5 × 10−5 to 2.0 × 10−36) with body mass index (BMI); 25 of these species were also found in the UK validation cohort. We found multiple associations
between urinary metabolites and BMI including urinary glycoproteins and N-acetyl
neuraminate (related to renal function), trimethylamine, dimethylamine,
4-cresyl sulfate, phenylacetylglutamine and
2-hydroxyisobutyrate (gut microbial
co-metabolites), succinate and citrate (tricarboxylic acid cycle
intermediates), ketoleucine
and the ketoleucine/leucine ratio (linked to
skeletal muscle mitochondria and branched-chain amino acid metabolism),
(skeletal muscle turnover), and
3-methylhistidine (skeletal muscle turnover and meat intake). We mapped
the multiple BMI-metabolite
relationships as part of an integrated systems
network that describes the connectivities between the complex pathway
and compartmental
signatures of human adiposity.

No comments: