Labrador study uncovers genetic ties to human obesity, highlighting shared pathways

Researchers studying British Labrador retrievers have identified multiple genes associated with canine obesity and shown that these genes are also associated with obesity in humans. The results are published in the journal Science.

The dog 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 was found to directly affect a brain pathway responsible for regulating the energy balance in the body, called the leptin melanocortin pathway.

An additional four genes associated with canine obesity, but which exert a smaller effect than DENND1B, were also mapped directly onto human genes.

“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 emphasize the importance of fundamental brain pathways in controlling appetite and body weight,” said Alyce McClellan in the University of Cambridge’s Department of Physiology, Development and Neuroscience, and joint first author of the report.

“We found that dogs at high genetic risk of obesity were more interested in food,” said Natalie Wallis of the University of Cambridge’s Department of Physiology, Development and Neuroscience, and joint first author of the report.

She added, “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.”

The study found that owners who strictly controlled their dogs’ diet and exercise managed to prevent even those with high genetic risk from becoming obese—but much more attention and effort was required.

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.

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.

“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.

She added, “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.”

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 analyzed 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.

The researchers then examined whether the genes they identified were relevant to human obesity. They looked at both large population-based studies, and at cohorts of patients with severe, early-onset obesity where single genetic changes are suspected to cause the 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 for their pets.

Raffan said, “This work shows how similar dogs are to humans genetically. Studying the dogs meant we had reason to focus on this particular gene, which has led to a big advance in understanding how our own brain controls our eating behavior and energy use.”

Researchers studying British Labrador retrievers have identified multiple genes associated with canine obesity and shown that these genes are also associated with obesity in humans. The results are published in the journal Science.

The dog 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 was found to directly affect a brain pathway responsible for regulating the energy balance in the body, called the leptin melanocortin pathway.

An additional four genes associated with canine obesity, but which exert a smaller effect than DENND1B, were also mapped directly onto human genes.

“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 emphasize the importance of fundamental brain pathways in controlling appetite and body weight,” said Alyce McClellan in the University of Cambridge’s Department of Physiology, Development and Neuroscience, and joint first author of the report.

“We found that dogs at high genetic risk of obesity were more interested in food,” said Natalie Wallis of the University of Cambridge’s Department of Physiology, Development and Neuroscience, and joint first author of the report.

She added, “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.”

The study found that owners who strictly controlled their dogs’ diet and exercise managed to prevent even those with high genetic risk from becoming obese—but much more attention and effort was required.

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.

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.

“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.

She added, “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.”

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 analyzed 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.

The researchers then examined whether the genes they identified were relevant to human obesity. They looked at both large population-based studies, and at cohorts of patients with severe, early-onset obesity where single genetic changes are suspected to cause the 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 for their pets.

Raffan said, “This work shows how similar dogs are to humans genetically. Studying the dogs meant we had reason to focus on this particular gene, which has led to a big advance in understanding how our own brain controls our eating behavior and energy use.”