Master gene

In a new scientific paper published on Sunday, a team of UK-based scientists have shown that a gene known as KLF14 can turn other genes in fat cells on and off. This "master switch" gene was previously known to be linked to type 2 diabetes and cholesterol levels.

These results, published in the journal Nature Genetics, could help in the search for treatment of obesity-linked diseases, such as type 2 diabetes.

"We didn't know what KLF14 was doing at all," Kerrin Small, a researcher from King's College London and one of the paper's co-authors, told Deutsche Welle. "Now we know how it particularly controls other genes in fat tissue."

As fat is said to play a key role in the susceptibility to metabolic diseases, this might be a possible target for future treatment.

"That was a pretty substantial step in understanding type 2 diabetes," said, Mark McCarthy, another Oxford researcher and co-author.

Master gene is able to turn genes on and off

"KLF14 is a transcription factor which circulates in fat cells and turns a whole set of genes on and off," he added. "So it's not doing something directly, it turns genes on and off that are affecting the risk of diabetes."

The scientists examined more than 20,000 genes in sub-cutaneous fat biopsies from 800 UK female twin volunteers. To confirm their findings, they examined another sample of 600 subcutaneous fat biopsies from Iceland.

McCarthy said there was striking evidence that KLF14 controls the expression levels of ten genes in fat tissue. These genes found to be controlled by this master switch gene are all linked to metabolism, including cholesterol, insulin, glucose levels and obesity in terms of body mass index. He added that other genes - "possibly in the hundreds" - might be affected as well.

The researchers say that all humans have the KLF14 gene, as it is always inherited from the mother. However, depending which variant a person has, influences the transcription factor in diferent ways, McCarthy said.

Which one is the crucial gene for diabetes?

"It's hard to intervene with drug treatment at this early stage," McCarthy warned, adding that they needed to understand first which of these genes that get turned off by KLF14 are the crucial ones that have an effect on increasing diabetes.

This view is echoed by Michael Stumvoll, the director of the department of endocrinology and nephrology at the University Hospital Leipzig who did not participate in the study, but shared his data as part of the study.

"It's definitely a breakthrough for system biologists and genetics, a huge step in terms of understanding the organization of genes involved in metabolism," he said in an interview with Deutsche Welle. "That's exactly what we need right now. It's important to know how genes depend on other genes."

"But this knowledge won't lead to a new treatment in the next five years. Maybe not even in the next 10 to 20 years and maybe it never will. It's a very complex matter, so there shouldn't be any uncritical tampering in a clinical context. You could do a lot of harm by shutting the wrong genes off."

Author: Sarah Steffen
Editor: Cyrus Farivar