Obesity, a disease of excess adipose tissue, is a serious health concern that increases the probability of various other health conditions. Worldwide there are more than 650 million people affected by this disease. Individuals with obesity are at a much higher risk of developing obesity-induced inflammatory and metabolic disturbances and subsequent type 2 diabetes (T2D). Currently, there are limited treatment options for obesity and T2D, therefore, new therapeutic targets derived from an increased understanding of disease mechanisms are a global health priority.
A study funded by the NIHR Imperial BRC, MRC and Welcome Trust has identified over 800 DNA switches that are changed in people with extreme obesity. These switches, known as epigenetic switches, are reversible and could hold the key to developing more effective treatments either for obesity or its harmful health consequences that follow. By comparing the fat cells of people with extreme obesity to those with normal body weight, the study found these epigenetic switches altered the activity of more than 500 genes, including genes with key roles in obesity and diabetes.
This study addressed key limitations of previous human epigenome-wide association studies (EWAS) (EWAS is an examination of a genome-wide set of quantifiable epigenetic marks, such as DNA methylation) in fat deposited under the skin and around the organs, such as the intestines, heart, and liver, with the aim to identify novel epigenetic mechanisms causing obesity or its adverse metabolic consequences.
Using cutting-edge computational techniques and CRISPR technology in fat cells, the researchers confirmed that a large fraction of these DNA switches directly contribute to obesity or conditions caused by obesity. The findings offer a significant step forward in understanding and addressing obesity at a genetic level, potentially revolutionising personalised treatments for this global health challenge.
The Imperial BRC Genomics Facility (supported by NIHR funding to the Imperial Biomedical Research Centre) provided resources and support that contributed to the RNA sequencing and targeted methylation sequencing results.