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Urine link

Urine link into how obesity causes disease

There are 29 different metabolic products whose levels correlated with the person's body mass index, and how they fit together in a complex network that links many different parts of the body

Scientists led by Imperial College London have identified chemical markers in urine associated with body mass, providing insights into how obesity causes disease. The research shows that obesity has a 'metabolic signature' detectable in urine samples, pointing to processes that could be targeted to mitigate its effects on health. The study, findings published in Science Translational Medicine, found multiple associations between urinary metabolites and BMI including urinary glycoproteins and N-acetyl neuraminate (related to renal function).

"Obesity has become a huge problem all over the world, threatening to overwhelm health services and drive life expectancy gains into reverse,” said Professor Jeremy Nicholson, Director of the MRC-NIHR National Phenome Centre at Imperial College London and a senior author of the study. “Tackling it is an urgent priority and it requires us to have a much better understanding of how body fat and other aspects of biology are related. These findings provide possible starting points for new approaches to preventing and treating obesity and its associated diseases."

It is known that urine contains a variety of chemicals known as metabolites, from a vast range of biochemical processes in the body. Technologies that analyse the metabolic makeup of a sample can therefore offer huge amounts of information that reflects both a person's genetic makeup and lifestyle factors.

The Imperial researchers analysed urine samples from over 2,000 volunteers in the US and the UK. They found 29 different metabolic products whose levels correlated with the person's body mass index, and how they fit together in a complex network that links many different parts of the body.

Some of these metabolites are produced by bacteria that live in the gut, highlighting the potentially important role these organisms play in obesity. Altered patterns of energy-related metabolites produced in the muscles were also identified as being linked to obesity.

They also found associations between urinary metabolites and 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), ethanolamine (skeletal muscle turnover), and 3-methylhistidine (skeletal muscle turnover and meat intake).

They also 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.

"Our results point to patterns of metabolic markers in the urine associated with obesity,” said Professor Paul Elliott, Head of the Department of Epidemiology and Biostatistics at Imperial. “It may be possible to identify non-obese people who have such patterns in their urine profile. These people could be at risk of developing obesity and metabolic diseases, and might benefit from personalised preventative interventions."

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