Novel gene discovered that helps keep some people thin

According to preliminary research, scientists may have found a gene that explains why some individuals stay slim.

The team found a variant of the ALK gene which is unique to thin individuals. The ALK gene codes for a protein, known as anaplastic lymphoma kinase, involved in cell growth. The variant was discovered after assessing clinical data and DNA samples from 47,102 Estonian individuals aged 20-44.

'We all know these people, who can eat whatever they want, they don't exercise, but they just don't gain weight. They make up around one percent of the population,' said senior author Professor Josef Penninger. 'We wanted to understand why. Most researchers study obesity and the genetics of obesity. We just turned it around and studied thinness, thereby starting a new field of research.'

Following this discovery, the team then began to investigate ALK function in mice and fly models. It is already known that particular ALK mutations can drive tumour development and can be found in numerous cancers. Hence, the findings suggest that it is a different mutation that causes resistance to weight gain and encourages thinness.

The team found that deleting the ALK gene resulted in thinner versions of both the mice and the flies. Furthermore, they were resistant to diet-induced and genetic-induced obesity. Professor Penninger explained: 'We gave the mice (what amounted to) a McDonald's diet. The normal mice got obese and the ones without ALK remained skinny'.

The future stages of the research will include understanding the regulation and expression of ALK in the brain at a molecular level, and how this promotes thinness. The team suggested in the paper, published in Cell, that ALK expression in hypothalamic neurons controls energy expenditure via the breakdown of fatty tissue, but this must be further investigated. It is also important to assess the data in greater, and more diverse, population groups.

It is hoped that the discovery could pave the way for helping source personalised treatments to tackle obesity. 'If you think about it, it's realistic that we could shut down ALK and reduce ALK function to see if we did stay skinny,' Professor Penninger said. 'ALK inhibitors are used in cancer treatments already. It's targetable. We could possibly inhibit ALK, and we actually will try to do this in the future.'