Obesity master gene discovered

A gene linked to type 2 diabetes and cholesterol levels is in fact a master regulator gene which controls the behaviour of other genes found within fat in the body.

Researchers from King’s College London and the University of Oxford have discovered that KLF14 is linked to a range of metabolic traits including body mass index and obesity, cholesterol, insulin and glucose levels – highlighting the interconnectedness of metabolic traits.

“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 Professor Tim Spector from the department of Twin Research at Kings.

Researchers examined over 20,000 genes in subcutaneous fat biopsies from 800 UK female twin volunteers, finding an association between KLF14 and the expression levels of multiple distant genes found in fat tissue. This was confirmed by a further independent sample of 600 biopsies from Icelandic subjects.

“KLF14 seems to act as a master switch controlling processes that connect changes in the behaviour of subcutaneous fat to disturbances in muscle and liver that contributes to diabetes and other conditions,” said Professor Mark McCarthy from Oxford.

KLF14 is special in that its activity is inherited from the mother – although each person inherits a copy of the gene from the mother and father, the copy from the father is switched off, a process known as imprinting. So the ability of KLF14 to control other genes is entirely dependent on the copy inherited from the mother.

The study was part of a large multinational collaboration funded by the Wellcome Trust known as MuTHER – Multiple Tissue Human Expression Resource Study – which aims to use the unique detailed genetic, genomic and phenotypic data generated to understand the mechanisms of how genes influence common age-related and metabolic diseases.