New research in the journal Science reports the discovery of new genes linked to obesity and shows that genetic predisposition to obesity can be over-ridden through exercise and a strict diet. Dr John Tadross from East Genomics contributed to this work, helping to show its relevance to obesity in humans.
Obesity genes in dogs and humans
Led by researchers at the University of Cambridge, the study focuses on Labrador dogs but uses genomic resources to show the same genes are relevant to human obesity. Dogs, like humans, are experiencing an obesity ‘epidemic’ and could similarly benefit from more understanding of the role of genetics in obesity.
About 40% of adult humans and 50% of pet dogs are overweight or obese. Dogs develop obesity through similar environmental influences as humans, and their genes can be more easily linked to disease due to low genetic diversity within breeds.
We managed to keep our Labrador, Max, in good shape despite his life-long love of food - but we really had to watch him whenever there was food around.
Yvonne, owner of Labrador Max
No single gene determines whether dogs or humans are prone to obesity. Their risk is a complex result of combining small effects from many different genes.
Of the genes found in the study, DENND1B had the largest effect on obesity in Labradors. The study also showed that DENND1B contributes to obesity in humans, as do four other genes identified in the dogs.
These genes are not immediately obvious targets for weight-loss drugs, because they control other key biological processes in the body that should not be interfered with. But the results emphasise the importance of fundamental brain pathways in controlling appetite and body weight.
Alyce McClellan in the University of Cambridge’s Department of Physiology, Development and Neuroscience (PDN)
On average, if a dog had a version of DENND1B that increased its obesity risk, its body fat was eight percent higher. As in humans, each dog can have up to two copies of the gene.
Dr John Tadross, molecular pathology clinical co-lead at East Genomics, helped to link the results from Labradors to equivalent genes in humans. In particular, he used HYPOMAP to show how DENND1B plays a role in regulating appetite.
Using large-scale single-cell human expression datasets like HYPOMAP, we were able to pinpoint how genes such as DENND1B influence appetite regulation in humans. This underscores how genomic computational tools can bridge the gap between genetic discoveries in animals and their implications for human health.
Dr John Tadross, Molecular Pathology Clinical Co-lead at East Genomics
In the study, data collected from dogs was linked to humans through large-scale population datasets, such as the UK Biobank, as well as individual cases of severe early-onset obesity thought to be caused by specific genetic changes.
Willpower can overcome genetics
Studying obesity in humans can be complex, as we are a diverse species and able to make our own decisions about food and exercise. Dog breeds have less genetic diversity, and owners have more control over how much their dog eats. This allows researchers to better separate the desire for food from the ability to get food.
By studying dogs we could measure their desire for food separately to the control owners exerted over their dog’s diet and exercise. In human studies, it’s harder to study how genetically driven appetite requires greater willpower to remain slim, as both are affecting the one person.
Dr Eleanor Raffan, a researcher in the University of Cambridge’s Department of PDN
The research found some dogs that maintained a healthy weight despite having genes that put them at a high risk of obesity. These dogs generally had owners who strictly controlled their dogs’ diet and exercise – but this required much more attention and effort than for dogs with lower obesity risk.
We measured how much dogs pestered their owners for food and whether they were fussy eaters. Dogs at high genetic risk of obesity showed signs of having higher appetite, as has also been shown for people at high genetic risk of obesity.
Natalie Wallis in the University of Cambridge’s Department of PDN
Similarly, people at high genetic risk of developing obesity will not necessarily become obese, if they follow a strict diet and exercise regime - but they are more prone to weight gain.
The researchers say owners can keep their dogs distracted from constant hunger by spreading out each daily food ration, for example by using puzzle feeders or scattering the food around the garden so it takes longer to eat, or by choosing a more satisfying nutrient composition.
My pet Labrador, Isla, eats absolutely everything and anything - litter, rabbit dropping, sticks, socks! It is hard to manage and the only way we keep her slim is regular beach trips.
Mike, owner of Labrador retriever Isla
The research was funded by Wellcome, the BBSRC and the Dogs Trust.