KLF14 Is “Master Switch” Gene for Obesity and Diabetes

A team of researchers, led by King's College London and the University of Oxford scientists, has found that a gene linked to type 2 diabetes and cholesterol levels is in fact a 'master regulator' gene, which controls the behavior of other genes found within fat in the body. As fat plays a key role in susceptibility to metabolic diseases such as obesity, heart disease, and diabetes, this study highlights the regulatory gene as a possible target for future treatments to fight these diseases. Published May 15, 2011, in Nature Genetics, the study was one part of a large multi-national collaboration funded by the Wellcome Trust, known as the MuTHER study. It involves researchers from King's College London, University of Oxford, The Wellcome Trust Sanger Institute, and the University of Geneva. DeCODE Genetics also contributed to the results reported in this paper. It was already known that the KLF14 gene is linked to type 2 diabetes and cholesterol levels but, until now, how it did this and the role it played in controlling other genes located farther away on the genome was unknown. The researchers examined over 20,000 genes in subcutaneous fat biopsies from 800 UK female twin volunteers. They found an association between the KLF14 gene and the expression levels of multiple distant genes found in fat tissue, which means it acts as a master switch to control these genes. This was then confirmed in a further independent sample of 600 subcutaneous fat biopsies from Icelandic subjects. These other genes found to be controlled by KLF14 are in fact linked to a range of metabolic traits, including body-mass index (obesity), and cholesterol, insulin, and glucose levels, highlighting the interconnectedness of metabolic traits. The KLF14 gene is special in that its activity is inherited from the mother. Each person inherits a set of all genes from both parents.
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