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New Genetic Variants for Obesity Discovered

  • April 9, 2024
  • 3 min read
New Genetic Variants for Obesity Discovered

Researchers at the University of Cambridge have identified rare variants in the BSN and APBA1 genes that increase the risk of severe adult-onset obesity. These are the first examples to effect only adults. Previously, obesity associated gene variants have been identified that raise the chance of childhood weight gain. These act in the brain via hypothalamic signalling of the hormones, leptin and melanocortin. These play a key satiety role in regulating food intake and energy expenditure. BSN and APBA1 do encode proteins found in the brain but these are not thought to be associated with the leptin-melanocortin pathway. Rather, it is thought by researchers that BSN and APBA1 play a role in the transmission of signals between brains cells. The theory is that as people who have these gene variants age, neurons in their brain start to degenerate, damaging key appetite regulating pathways.

This new mechanism of weight gain will help scientists better understand the neural biology of obesity, providing potential drug targets to treat it in the future.

The BSN gene, also known as Bassoon, can raise the risk of obesity by as much as 6 times. It is also associated with an increased risk of type 2 diabetes and fatty liver disease. This is thought to affect 1 in 6,500 adults. In the UK this would equate to 10,000 people. The variants in the gene APBA1 also increase obesity risk but at a nominally significant rate.

Professor Giles Yeo, study author based at the MRC Metabolic Diseases Unit, says “We have identified two genes with variants that have the most profound impact on obesity risk at a population level we’ve ever seen, but perhaps more importantly, that the variation in Bassoon is linked to adult-onset and not childhood obesity. Thus these findings give us a new appreciation of the relationship between genetics, neurodevelopment and obesity.”

Obesity is a multifactorial and complex disease resulting from interactions between genetic predisposition and environmental factors. Although carrying a certain combination of gene variants may increase risk factors, controlling the environment can still go a long way to mitigating the chance of becoming obese. In the past few years we have seen an increasing number of scientists and doctors speaking out about how our food environment is contributing to the obesity epidemic. The prevalence of cheap, available, hyperpalatable ultra processed food (UPF) is a leading cause of weight gain in the UK, regardless of peoples genetics. In his book, “Ultra Processed People”, Dr Chris van Tulleken argues that the main reason for the rapid increase in the obesity, especially since the 1980’s, is “the correspondingly rapid increase in production and consumption of ultra-processed food and drink products.”

For people who do carry these variants, it is much harder to regulate appetite, making them more vulnerable to overeating. This is only compounded by the effects of UPF and they are more likely to experience severe outcomes. Society tends to harshly regard overweight people, stereotyping them as lazy or greedy. Knowing there is a strong biological factor will hopefully lead to the destigmatisation of obesity.

Giles Yeo explains, “People living with obesity are not bad, slothful or morally bereft, they are fighting their biology,” says Yeo. “Until we in society, including those responsible for policy, understand this, we will never come up with a cogent and sustainable solution to the obesity problem.”

About Author

Natalie Shanahan

Natalie Shanahan has a BSc in Genetics and a MSc in Bioinformatics. She worked as a lecturer, teaching genetics and biochemistry, before moving to Australia to work for their first Bioinformatics company. Here she managed their marketing as well as working on their numerous educational resources. Natalie left her career in science to follow her passion and now works as a personal trainer and nutrition consultant, helping individuals and employees of large organisations, better understand their health and wellbeing.

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