Single molecule could hold the key to tackling obesity, study finds

30 January 2024 | Muriel Cozier

‘We may be able to help treat or prevent obesity by targeting the RaIA pathway with new therapies.’

Researchers from the University of California San Diego School of Medicine have discovered a link between obesity and the functioning of mitochondria, essential for the production of energy.

Publishing their work in Nature Metabolism, researchers found that mitochondria in the fat cells of mice fed with a high-fat diet broke apart into smaller mitochondria, with a reduced capability to burn fat. They discovered that this process is controlled by a single gene, and deleting this gene allowed the mice to be protected from excess weight gain, even on the same high-fat diet.

Obesity is said to affect more than 40% of the US population and it is postulated that the condition, which impacts the ability of cells to burn energy, is why it is difficult for people with obesity to lose fat. Understanding how these metabolic abnormalities start has been a mystery to scientists.

The researchers now believe that a molecule called RaIA could be implicated in the onset and development of obesity. The molecule has a number of functions including the breakdown of mitochondria when they malfunction. It is believed that when this molecule is overactive, it interferes with the normal functioning of mitochondria, triggering the metabolism issues associated with obesity. Deleting the gene associated with this molecule protected the mice from ‘diet induced weight gain’.

‘In essence, chronic activation of RaIA appears to play a critical role in suppressing energy expenditure in obese adipose tissue,’ said Alan Saltiel, PhD Professor In the Department of Medicine at UC San Diego School of Medicine. ‘The gene we identified is a critical part of that transition from healthy weight to obesity,’ Professor Saltiel added.

Researchers also found that some of the proteins affected by RaIA in mice are compatible in certain respects to human proteins that are associated with obesity and insulin resistance, suggesting similar mechanisms may be driving human obesity.

‘We may be able to help treat or prevent obesity by targeting the RaIA pathway with new therapies. We’re only just beginning to understand the complex metabolism of this disease, but the future possibilities are exciting,’ Professor Saltiel said.

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