19th July 2022 – King’s College London

Changes that occur in the body in response to an increase in belly fat have been put under the microscope as part of a study from TwinsUK, offering new insight into the cause of metabolic disease.

The study, led by King’s College London researchers Dr Jordana Bell and Colette Christiansen and published in the medical journal Genome Medicine, looked at how epigenetic marks (measures of how the human body reads DNA to affect the way genes work) in fat tissue change as belly fat accumulates.

Using samples from 538 TwinsUK participants and combining genetic, gene function, diet, and health data, the researchers examined epigenetic marks across the genome (the complete set of a person’s genetic material) and found nine genes that are highly relevant to metabolic disease risk.

Among these was a gene where the identified epigenetic changes were recognised as a potential mechanism through which diet can affect belly fat accumulation, as well as other epigenetic marks that translate genetic risk effects on metabolic health.

The findings also allowed the researchers to characterise the molecular changes that occur because of an increase in belly fat and the impact these changes have on gene function and insulin resistance.

Dr Jordana Bell, reader in Epigenomics in the School of Life Course & Population Sciences said:

“With rapidly rising rates of obesity worldwide, it is important that we understand how elevated body fat affects us at the molecular level and how this translates to metabolic disease risk,”

Metabolic diseases – the most common of which is diabetes – disrupt normal metabolism or the process of converting food to energy on a cellular level.

While previous studies in this field have explored the role of epigenetic marks in overall obesity using body mass index (BMI), the build-up of belly fat deep within the abdomen is known to be a greater risk factor for metabolic disease than BMI alone.

Dr Jordana Bell added:

“Our study brings us one step closer to this goal by identifying an epigenetic signature of excess belly fat, understanding its genetic and dietary triggers, and characterising its functional impacts and clinical consequences for insulin resistance,”

Based on the results of the study, the researchers also developed an epigenetic predictor of insulin resistance, relating their findings to the clinical consequences of elevated belly fat.

Colette Christiansen, PhD researcher in the School of Life Course & Population Sciences said:

“It is exciting to see that when we combine many different layers of biological information, we can start to unravel the mechanisms which drive the state of our biological health.”