̽��ֱ�� of Cambridge - Eleanor Raffan

Scientists identify genes that make humans and Labradors more likely to become obese

jg533 — Thu, 06 Mar 2025 19:03:04 +0000

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.

̽��ֱ��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 emphasise the importance of fundamental brain pathways in controlling appetite and body weight,” said Alyce McClellan in the ̽��ֱ�� 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 in the ̽��ֱ�� 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.”

̽��ֱ��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.

̽��ֱ��results were published on 6 March in the journal 'Science'.

“Studying the dogs showed us something really powerful: owners of slim dogs are not morally superior. ̽��ֱ��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 ̽��ֱ�� 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.”

̽��ֱ��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.

̽��ֱ��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.

̽��ֱ��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 behaviour and energy use.”

̽��ֱ��research was funded by Wellcome, the BBSRC, Dogs Trust, Morris Animal Foundation, MRC, France Genomique consortium, European Genomic Institute for Diabetes, French National Center for Precision Diabetic Medicine, Royal Society, NIHR, Botnar Foundation, Bernard Wolfe Health Neuroscience Endowment, Leducq Fondation, Kennel Club Charitable Trust.

Reference
Wallis, N J et al: ‘Canine genome-wide association study identifies DENND1B as an obesity gene in dogs and humans.’ Science, March 2025. DOI: 10.1126/science.ads2145

Researchers at the ̽��ֱ�� of Cambridge have discovered genes linked to obesity in both Labradors and humans. They say the effects can be over-ridden with a strict diet and exercise regime.

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

James Barker on Unsplash

Labrador licking nose

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Genetic mutation in a quarter of all Labradors hard-wires them for obesity

jg533 — Wed, 06 Mar 2024 19:06:36 +0000

This obesity-driving combination means that dog owners must be particularly strict with feeding and exercising their Labradors to keep them slim.

̽��ֱ��mutation is in a gene called POMC, which plays a critical role in hunger and energy use.

Around 25% of Labradors and 66% of flatcoated retriever dogs have the POMC mutation, which researchers previously showed causes increased interest in food and risk of obesity.

̽��ֱ��new study reveals how the mutation profoundly changes the way Labradors and flatcoated retrievers behave around food. It found that although they don’t need to eat more to feel full, they are hungrier in between meals.

In addition, dogs with the POMC mutation were found to use around 25% less energy at rest than dogs without it, meaning they don’t need to consume as many calories to maintain a healthy body weight.

“We found that a mutation in the POMC gene seems to make dogs hungrier. Affected dogs tend to overeat because they get hungry between meals more quickly than dogs without the mutation,” said Dr Eleanor Raffan, a researcher in the ̽��ֱ�� of Cambridge’s Department of Physiology, Development and Neuroscience who led the study.

She added: “All owners of Labradors and flatcoated retrievers need to watch what they’re feeding these highly food-motivated dogs, to keep them a healthy weight. But dogs with this genetic mutation face a double whammy: they not only want to eat more, but also need fewer calories because they’re not burning them off as fast.”

̽��ֱ��POMC mutation was found to alter a pathway in the dogs’ brains associated with body weight regulation. ̽��ֱ��mutation triggers a starvation signal that tells their body to increase food intake and conserve energy, despite this being unnecessary.

̽��ֱ��results are published today in the journal Science Advances.

Raffan said: “People are often rude about the owners of fat dogs, blaming them for not properly managing their dogs’ diet and exercise. But we’ve shown that Labradors with this genetic mutation are looking for food all the time, trying to increase their energy intake. It’s very difficult to keep these dogs slim, but it can be done.”

̽��ֱ��researchers say owners can keep their retrievers distracted from this 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.

In the study, 87 adult pet Labrador dogs - all a healthy weight or moderately overweight - took part in several tests including the ‘sausage in a box’ test.

First, the dogs were given a can of dogfood every 20 minutes until they chose not to eat any more. All ate huge amounts of food, but the dogs with the POMC mutation didn’t eat more than those without it. This showed that they all feel full with a similar amount of food.

Next, on a different day, the dogs were fed a standard amount of breakfast. Exactly three hours later they were offered a sausage in a box and their behaviour was recorded. ̽��ֱ��box was made of clear plastic with a perforated lid, so the dogs could see and smell the sausage, but couldn’t eat it.

̽��ֱ��researchers found that dogs with the POMC mutation tried significantly harder to get the sausage from the box than dogs without it, indicating greater hunger.

̽��ֱ��dogs were then allowed to sleep in a special chamber that measured the gases they breathed out. This revealed that dogs with the POMC mutation burn around 25% fewer calories than dogs without it.

̽��ֱ��POMC gene and the brain pathway it affects are similar in dogs and humans. ̽��ֱ��new findings are consistent with reports of extreme hunger in humans with POMC mutations, who tend to become obese at an early age and develop a host of clinical problems as a result.

Drugs currently in development for human obesity, underactive sexual desire and certain skin conditions target this brain pathway, so understanding it fully is important.

A mutation in the POMC gene in dogs prevents production of two chemical messengers in the dog brain, beta-melanocyte stimulating hormone (β-MSH) and beta-endorphin, but does not affect production of a third, alpha-melanocyte stimulating hormone (α-MSH).

Further laboratory studies by the team suggest that β-MSH and beta-endorphin are important in determining hunger and moderating energy use, and their role is independent of the presence of α-MSH. This challenges the previous belief, based on research in rats, that early onset human obesity due to POMC mutations is caused only by a lack of α-MSH. Rats don’t produce beta-melanocyte stimulating hormone, but humans and dogs produce both α- and β-MSH.

̽��ֱ��research was funded by ̽��ֱ��Dogs Trust and Wellcome.

Reference: Dittmann, M T et al: ‘Low resting metabolic rate and increased hunger due to β-MSH and β-endorphin deletion in a canine model.’ Science Advances, March 2024. DOI: 10.1126/sciadv.adj3823

New research finds around a quarter of Labrador retriever dogs face a double-whammy of feeling hungry all the time and burning fewer calories due to a genetic mutation.

Labradors with this genetic mutation are looking for food all the time, trying to increase their energy intake. It’s very difficult to keep these dogs slim, but it can be done.

Eleanor Raffan

A quarter of Labradors are hard-wired for obesity

Jane Goodall

Labrador retriever dog

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Genetic variant may help explain why Labradors are prone to obesity

cjb250 — Tue, 03 May 2016 15:57:14 +0000

In developed countries, between one and two in three dogs (34-59%) is overweight, a condition associated with reduced lifespan, mobility problems, diabetes, cancer and heart disease, as it is in humans. In fact, the increase in levels of obesity in dogs mirrors that in humans, implicating factors such as reduced exercise and ready access to high calorie food factors. However, despite the fact that dog owners control their pets’ diet and exercise, some breeds of dog are more susceptible to obesity than others, suggesting the influence of genetic factors. Labradors are the most common breed of dog in the UK, USA and many other countries worldwide and the breed is known as being particularly obesity-prone.

In a study published today in the journal Cell Metabolism, an international team led by researchers at the Wellcome Trust-Medical Research Council Institute of Metabolic Science, ̽��ֱ�� of Cambridge, report a study of 310 pet and assistance dog Labradors. Independent veterinary professionals weighed the dogs and assessed their body condition score, and the scientists searched for variants of three candidate obesity-related genes. ̽��ֱ��team also assessed ‘food motivation’ using a questionnaire in which owners reported their dog’s behavior related to food.

̽��ֱ��researchers found that a variant of one gene in particular, known as POMC, was strongly associated with weight, obesity and appetite in Labradors and flat coat retrievers. Around one in four (23%) Labradors is thought to carry at least one copy of the variant. In both breeds, for each copy of the gene carried, the dog was on average 1.9kg heavier, an effect size particularly notable given the extent to which owners, rather than the dogs themselves, control the amount of food and exercise their dogs receive.

“This is a common genetic variant in Labradors and has a significant effect on those dogs that carry it, so it is likely that this helps explain why Labradors are more prone to being overweight in comparison to other breeds,” explains first author Dr Eleanor Raffan from the ̽��ֱ�� of Cambridge. “However, it’s not a straightforward picture as the variant is even more common among flat coat retrievers, a breed not previously flagged as being prone to obesity.”

̽��ֱ��gene affected is known to be important in regulating how the brain recognises hunger and the feeling of being full after a meal. “People who live with Labradors often say they are obsessed by food, and that would fit with what we know about this genetic change,” says Dr Raffan.

Senior co-author Dr Giles Yeo adds: “Labradors make particularly successful working and pet dogs because they are loyal, intelligent and eager to please, but importantly, they are also relatively easy to train. Food is often used as a reward during training, and carrying this variant may make dogs more motivated to work for a titbit.

“But it’s a double-edged sword – carrying the variant may make them more trainable, but it also makes them susceptible to obesity. This is something owners will need to be aware of so they can actively manage their dog’s weight.”

̽��ֱ��researchers believe that a better understanding of the mechanisms behind the POMC gene, which is also found in humans, might have implications for the health of both Labradors and human.

Professor Stephen O’Rahilly, Co-Director of the Wellcome Trust-Medical Research Council Institute of Metabolic Science, says: “Common genetic variants affecting the POMC gene are associated with human body weight and there are even some rare obese people who lack a very similar part of the POMC gene to the one that is missing in the dogs. So further research in these obese Labradors may not only help the wellbeing of companion animals but also have important lessons for human health.”

̽��ֱ��research was funded by the Wellcome Trust, the Medical Research Council and the Dogs Trust.

Reference
Raffan, E et al. A deletion in the canine POMC gene is associated with weight and appetite in obesity prone Labrador retriever dogs. Cell Metabolism; 3 May 2016; DOI: 10.1016/j.cmet.2016.04.012

A genetic variation associated with obesity and appetite in Labrador retrievers – the UK and US’s favourite dog breed – has been identified by scientists at the ̽��ֱ�� of Cambridge. ̽��ֱ��finding may explain why Labrador retrievers are more likely to become obese than dogs of other breeds.

People who live with Labradors often say they are obsessed by food, and that would fit with what we know about this genetic change

Eleanor Raffan

Thomas Hawk

Where's My Snacks? (crop)

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