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Metabolomic Study Uncovers Obesity-Related Urine Signature

NEW YORK (GenomeWeb) – In Science Translational Medicine, an international team led by investigators at Imperial College London introduced a set of urine metabolites that seems to coincide with obesity.

As part of the International Study of Macro- and Micronutrients and Blood Pressure, or INTERMAP, the team used a combination of nuclear magnetic resonance spectroscopy and ion exchange chromatography to track metabolite patterns in urine samples from nearly 1,900 individuals over two 24-hour stretches spaced out by three weeks.

The researchers' comparison of these urine metabolite patterns with participant body mass index patterns revealed a relationship between BMI status levels of a few dozen metabolites — findings they followed up on in a group of more than 400 individuals from the UK.

"[O]ur results captured the metabolic signatures of the multitude of dietary, environmental, and other lifestyle characteristics associated with obesity," senior author Jeremy Nicholson, director of the Imperial College London's MRC-National Institute for Health Research National Phenome Centre, and his colleagues wrote. 

In a statement, Nicholson said such findings "provide possible starting points for new approaches to preventing and treating obesity and its associated diseases."

INTERMAP researchers collected urine samples from participants over the course of a day and again several weeks later.

For the current analysis, the team pooled urine samples collected from each of the individuals in a given 24-hour stretch, subjecting these samples to NMR spectroscopy to get an unbiased look at urine compounds.

The researchers also did targeted ion exchange chromatography-based testing on the samples, focusing on branched-chain and other amino acids, which are suspected of playing a role in adiposity.

In each individual, samples collected three weeks apart tended to contain similar sets of metabolites. And at least some of those metabolites corresponded with adiposity, the team reported.

From unbiased NMR-based metabolite profiling of the discovery cohort, a group that consisted of 962 men and 918 women from the US, the researchers found 29 metabolites that were detected at different levels depending on an individual's obesity.

That set — which included metabolites produced through gut microbe-host co-metabolism, as well as compounds associated with skeletal muscle turnover, kidney function, and other metabolic processes — was also tested in urine samples from 444 individuals from the UK.

After the validation step, 25 of the metabolites remained linked to obesity, researchers noted. They also saw BMI associations for most of the amino acids and amino acid-related metabolites tested by targeted ion exchange chromatography analyses.

In heavier individuals, for example, the team saw lower-than-usual proportions of an amino acid derivative called ketoleucine, formed from leucine in muscle in response to exercise, in individuals with elevated BMIs. On the other hand, urine levels of glycoproteins tended to creep up in conjunction with growing girth.

"Our findings reveal multiple connections between many metabolic compartments and pathways, and provide possible starting points for new approaches to prevention and treatment," the study's authors concluded, "for example, functional microbiome modulation and stimulation of skeletal muscle mitochondrial metabolism."