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‘Skinny’ Genes Could Help Tackle Obesity Crisis

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For many individuals who find the shape and size of their body a real cause of insecurity and anxiety, this time of year can prove challenging.  The customary new year’s resolution to get fit and healthy means that the wrath of diet culture is stronger than ever. Billboards and Facebook timelines are adorned with familiar advertisements for heavily reduced gym memberships, sales on protein powder (if purchased in bulk, of course), and amazing savings on blenders.

As human beings we tend to fret about how we can change, contour, sculpt and control our body shape. But what if our ability to do so is actually out of our hands?

Have you ever met an individual able to consume a substantial number of calories without ever showing as much as a pound in weight gain? In the largest study of its kind to date, researchers from the University of Cambridge have explored why certain people are able to maintain a ‘thin’ figure almost effortlessly, whilst others gain weight extremely easily. The answer? It’s in your genes.

Previous twin studies have illustrated that weight variation is largely influenced by genetics. However, until recently the research field has been dominated by studies focusing on individuals that are overweight. The Study Into Lean and Thin Subjects – STILTS – established by Professor Sadaf Farooqi at the Wellcome-MRC Institute of Metabolic Science, used a sample cohort of 2,000 ‘thin’ people, defined as an individual with a body mass index (BMI) of less than 18kg/m2,  and aimed to examine why and how some people find it easier to stay thin than others.

Advancing this work in a study published January 24 in PLOS Genetics, Professor Farooqi’s team collaborated with Dr Inês Barroso’s team at the Wellcome Sanger Institute. In total, they compared the DNA of 14,000 people; including 1,622 thin volunteers from the STILTS cohort, 1,985 severely obese people and a further 10,433 normal weight controls. A normal weight was defined as a BMI in the range of 19-30m2.

Why do we look to our genes to reveal information about our body size? Put simply, our DNA is comprised of genes encoding proteins that carry out certain functions within our body. If there is a subtle change in the gene, known as a genetic variant, a completely different protein can be produced and consequently the function of the protein in the body is changed. If this protein is involved in the body’s metabolism for example, then the genetic variant may affect how we process, digest and store food.

Professor Farooqi and team identified common genetic variants that had previously been highlighted as increasing an individual’s chance of being obese. However, they also discovered novel genetic regions associated with being thin. From this information, the scientists created a genetic risk score to see what impact the genetic variants had on a person’s weight.

Interestingly, thin people were found to have a drastically lower genetic risk score, meaning they had fewer genetic variants associated with increasing an individual’s likelihood of being overweight.

Speaking in a recent press release Farooqi said, “This research shows for the first time that healthy thin people are generally thin because they have a lower burden of genes that increase a person’s chances of being overweight and not because they are morally superior, as some people like to suggest.”

“We already know that people can be thin for different reasons” Farooqi adds. “Some people are just not that interested in food whereas others can eat what they like, but never put on weight. If we can find the genes that prevent them from putting on weight, we may be able to target those genes to find new weight loss strategies and help people who do not have this advantage.”

Reference: Riveros-Mckay et al. 2019. Genetic architecture of human thinness compared to severe obesity. PLOS Genetics. https://doi.org/10.1371/journal.pgen.1007603.