Scientists identify genes that make humans and Labrador retrievers more likely to develop obesity
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Researchers studying a population of pet British Labrador retrievers have identified multiple genes associated with canine obesity and show that these genes are also associated with obesity in humans.
The results are published today in the journal Science, and the research project was funded by Wellcome, the BBSRC and the Dogs Trust.
"The genetic basis of obesity is often overlooked because of the environmental factors also involved. However, we know that obesity is a highly heritable disease in people, and our study shows that the same is true in dogs!" said the University of Liverpool’s Dr Natalie Wallis (who undertook this research in her previous role in the University of Cambridge’s Department of Physiology, Development and Neuroscience), joint first author of the report.
The gene found to be most strongly associated with obesity in Labradors is called DENND1B. Humans also carry the DENND1B gene, and the researchers found that this gene is also linked with obesity in people.
DENND1B directly affects a brain pathway responsible for regulating the energy balance and appetite in the body, called the leptin-melanocortin pathway.
An additional four genes associated with canine obesity were mapped directly onto human genes, but these appear to exert a smaller effect on obesity than DENND1B,.
“These genes are not immediately obvious targets for weight-loss drugs, because they control many other key biological processes in the body that should not be interfered with. Nevertheless, the results emphasise the importance of fundamental brain pathways in controlling appetite and body weight,” said Dr Alyce McClellan in the University of Cambridge’s Department of Physiology, Development and Neuroscience, and joint first author of the report.
The researchers also measured dogs’ behaviour around food. “Dogs at high genetic risk of obesity also had bigger appetites, something that is also seen with people at high genetic risk of obesity,” said Dr Natalie Wallis.
The study found that owners who strictly controlled their dogs’ diet and exercise could prevent even those with high genetic risk from developing obesity, although it required more attention and effort.
Similarly, people at high genetic risk of developing obesity are more prone to weight gain, but will not necessarily become obese, if they are able to follow a strict diet and exercise regime.
As with human obesity, no single gene determined whether the dogs were prone to obesity; the net effect of multiple genetic variants determined whether dogs were at high or low risk.
Dr Natalie Wallis added: “Interestingly, our research demonstrates the difference in obesity risk between Labradors of different coat colours is due, at least in part, to genetics. Chocolate Labrador retrievers are more genetically susceptible to obesity, compared with Labradors with different coat colours. I think this will be really insightful for dog owners.”
The current human obesity epidemic is mirrored by an obesity epidemic in dogs. About 40-60% of pet dogs are overweight or obese, which can lead to a range of health problems.
Dogs are a good model for studying human obesity: they develop obesity through similar environmental influences as humans, and because dogs within any given breed have a high degree of genetic similarity, their genes can be more easily linked to disease.
To get their results, the researchers recruited owners with pet dogs in which they measured body fat, scored ‘greediness’, and took a saliva sample for DNA. Then they analysed the genetics of each dog. By comparing the obesity status of the dog to its DNA, they could identify the genes linked to canine obesity.
Dogs carrying the genetic variant most associated with obesity, DENND1B, had around 8% more body fat than those without it.
“Studying the dogs showed us something really powerful: owners of slim dogs are not morally superior. The same is true of slim people. If you have a high genetic risk of obesity, then when there’s lots of food available you’re prone to overeating and gaining weight unless you put a huge effort into not doing so,” said Dr Eleanor Raffan, a researcher in the University of Cambridge’s Department of Physiology, Development and Neuroscience who led the study.
The University of Liverpool’s Professor Alex German also contributed to this study. Professor German and colleagues recently had a related article published in Veterinary Record discussion recent advances in definition of obesity in humans and how such definitions can be adapted for cats and dogs. You can read the article here: https://bvajournals.onlinelibrary.wiley.com/doi/10.1002/vetr.5300
Adapted from a press release by the University of Cambridge. Image credit: University of Cambridge.