Gene variant that helps regulate body weight discovered

The discovery that a gene variant affects appetite control could lead to new strategies for treating obesity.

The variant, found in the ZFHX3 gene, was previously linked to lower BMI and occurs naturally in about four percent of people. However, the mechanism by which it affects body weight was not understood.

'There is a big genetic component related to our appetite and growth but it's not fully understood,' said Dr Rebecca Dumbell, from Nottingham Trent University, who is corresponding author of the research published by the Federation of American Societies for Experimental Biology. 'Understanding what is happening in those who have the mutation paves the way to exploring potential new weight loss intervention targets for all people.'

Dr Dumbell and colleagues at Medical Research Council Harwell Institute in Oxfordshire and the University of Aberdeen used a mouse model to find out how the variant affects body mass.

Compared to mice with the two normal copies of ZFHX3, mice carrying the variant ate 12 percent less, and weighed around 20 percent less at age one. They also had lower fat mass, and produced lower levels of the hormones insulin (which is associated with blood sugar regulation) and leptin (which helps regulate hunger).

The researchers found that ZFHX3 is active in the hypothalamus, where produces a protein that appears to influence expression of a number of other genes. The hypothalamus is a part of the brain which regulate body processes such as body temperature, sleep, hunger and thirst through a complex network of hormones.

The protein produced by the variant form of ZFHX3 was shown to differently affect gene expression in the brain, and that the changes appeared to be in genes associated with weight regulation.

Dr Dumbell has already secured funding for the next stage of her research: 'Our future work will look at how the ZFHX3 gene acts in key parts of the brain, this will help narrow down exactly how it works to change how much the mice eat, or how fast their metabolism is,' she told The Independent. 'Understanding how this works will (also) allow us to understand how different people might struggle more to maintain a "healthy" weight.'