Study: How a ‘Fat Gene’ Affects Cholesterol and Diabetes

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Scientists have long known that obesity is associated with a host of other health conditions, including Type 2 diabetes and heart disease. Now a team of researchers at King’s College London and the University of Oxford have shed light on why: a gene found in fat tissue acts as a “master regulator,” controlling the effect of a bunch of other genes that are linked to obesity, cholesterol and diabetes.

The master gene in question is called KLF14, and while it has previously been linked to Type 2 diabetes and cholesterol, the new research clarifies how — and offers a new target for treatment of obesity-related diseases.

“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,” said lead author Tim Spector in a statement.

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The research was part of a large-scale multinational study called the MuTHER study (for Multiple Tissue Human Expression Resource). Scientists analyzed more than 20,000 genes found in fat samples taken from just under the skin of 400 pairs of female twins in the U.K. They found an association between KLF14 and the expression of other genes, also found in fat, that affect a range of metabolic traits including body-mass index, cholesterol and insulin and glucose levels.

To confirm the findings, the researchers further tested 600 fat samples from a separate group of Icelandic women.

Interestingly, the researchers say, the activity of the KLF14 gene is inherited from the mother; the copy of the gene inherited from the father is switched off. So how a person’s KLF14 gene may affect expression of other metabolism-related genes is dependent on the copy received from the mother.

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The findings further corroborate existing evidence that metabolic traits — everything from weight to insulin levels are interrelated — and that those relationships have a genetic component.

The researchers hope their discovery will spur further research and someday help improve medical treatments for obesity and its associated metabolic diseases. “This has great therapeutic potential,” said Spector. “By studying large detailed populations such as the twins we hope to find more of these regulators.”

The study was published in Nature Genetics on May 15.