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Master gene found that drives diabetes and obesity

Kathleen Blanchard's picture
Obesity, diabetes gene

One gene, passed from mothers to siblings, controls cholesterol, obesity and related diseases.

King's College London and the University of Oxford researchers have discovered the KLF14 is the single regulator of distant fat genes in the body that controls how other genes behave.

According to Tim Spector from the Department of Twin Research at King's, who led the research, dubbed the MuTHER project, "This is the first major study that shows how small changes in one master regulator gene can cause a cascade of other metabolic effects in other genes."

Spector says the finding opens the door for discovery of other master genes that lead to disease. Targeting the genetic culprit for obesity and other chronic diseases could change prevention and treatment approaches.

Active KLF14 obesity gene passed from mothers

The gene is unique, say the scientists. Full sets of genes are passed from both parents, but in the case of the KLF14 gene, activity is inherited from the mother. The gene inherited from the father is inactive, and has no effect for contributing to the way fat genes behave to cause high cholesterol that leads to heart disease and obesity that contributes to type 2 diabetes.

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Professor Mark McCarthy from the University of Oxford, who co-led the study said the master switch gene affects the way subcutaneous fat is distributed in the body to contribute to metabolic disorders.

For the study, scientists studied 20,000 genes in subcutaneous fat from biopsies of 800 UK female twins who volunteered for the research.

They compared the finding that the KLF14 gene regulates distant fat genes in samples of 600 subcutaneous fat biopsies from study volunteers in Iceland.

The authors say they already knew the KLF14 gene contributed to diseases like obesity and diabetes, but until now they had no idea it was the master regulator of other genes found in fat.

Finding the "master switch" gene responsible for controlling distant fat genes could lead to targeted therapy that interrupts the genetic pathways driving high cholesterol, diabetes and obesity.

Nature Genetics (2011) doi:10.1038/ng.833
“Identification of an imprinted master trans regulator at the KLF14 locus related to multiple metabolic phenotypes”
Kerrin S Small, et al.
May, 2011