Scientists identify genes that make humans and Labradors more likely to become obese
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 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 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 in 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.
The results are published today in the journal 'Science'.
“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 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.
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 behaviour and energy use.”
The 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 University 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 WallisJames Barker on UnsplashLabrador licking nose
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Map of brain’s appetite centre could enable new treatments for obesity and diabetes
Published today in Nature, this comprehensive resource, called HYPOMAP, provides an unparalleled view of the brain’s appetite centre and promises to accelerate the development of treatments for obesity and diabetes.
The hypothalamus is often described as the brain’s ‘control centre’, orchestrating many of the body’s most vital processes. While much of our knowledge of the hypothalamus comes from animal studies, especially in mice, translating these findings to humans has long been a challenge. HYPOMAP bridges this gap by providing an atlas of the individual cells within the human hypothalamus. This resource not only charts over 450 unique cell types but also highlights key differences between the human and mouse hypothalamus — differences that have major implications for drug development.
“This is a game-changer for understanding the human hypothalamus,” said Professor Giles Yeo, senior author of the study from the Institute of Metabolic Science-Metabolic Research Laboratories (IMS-MRL) and MRC Metabolic Diseases Unit, University of Cambridge.
“HYPOMAP confirms the critical role of the hypothalamus in body-weight regulation and has already allowed us to identify new genes linked to obesity. It gives us a roadmap to develop more effective, human-specific therapies.”
Together with researchers at the Max Planck Institute for Metabolism Research in Cologne, Professor Yeo and colleagues used cutting-edge technologies to analyse over 400,000 cells from 18 human donors. HYPOMAP allows researchers to pinpoint specific cell types, understand their genetic profiles, and explore how they interact with neighbouring cells. This detailed cellular resolution offers invaluable insights into the circuits that regulate appetite and energy balance, as well as other functions such as sleep and stress responses.
Comparison with a mouse hypothalamus atlas revealed both similarities and critical differences. Notably, some neurons in the mouse hypothalamus have receptors for GLP-1 — targets of popular weight-loss drugs like semaglutide — that are absent in humans.
"While drugs like semaglutide have shown success in treating obesity, newer therapies target multiple receptors such as GLP-1R and GIPR. Understanding how these receptors function specifically in the human hypothalamus is now crucial for designing safer and more effective treatments," said Dr Georgina Dowsett from the Max Planck Institute for Metabolism Research and formerly at the IMS-MRL.
“Our map of the human hypothalamus is an essential tool for basic and translational research,” added Professor Jens C. Brüning, Director at the Max Planck Institute. “It allows us to pinpoint which mouse nerve cells are most comparable to human cells, enabling more targeted preclinical studies.”
HYPOMAP’s open-access nature ensures that it will be an invaluable resource for scientists worldwide. By offering insights into the hypothalamus’s role in conditions ranging from obesity to cachexia (a wasting condition associated with several illness, which involves extreme loss of muscle and fat), it provides a foundation for tackling some of the most pressing health challenges of our time.
Dr John Tadross, Consultant Pathologist at Addenbrooke’s Hospital and lead author from IMS-MRL, said: “This is just the beginning. The atlas itself is a milestone, but what could really make a difference for patients is understanding how the hypothalamus changes in people who are overweight or underweight. This could fundamentally shift our approach to metabolic health and enable more personalised therapies.”
With HYPOMAP, researchers have a new tool to unlock the secrets of the human brain’s metabolic control centre. By better understanding the human hypothalamus, science takes a significant step toward combating obesity, diabetes, and related conditions.
Reference
Tadross, JA, Steuernagel, L & Dowsett, GKC et al. A comprehensive spatio-cellular map of the human hypothalamus. Nature; 5 Feb 2025; DOI: 10.1038/s41586-024-08504-8
Adapted from a story by the Institute of Metabolic Science-Metabolic Research Laboratories and the Max Planck Institute for Metabolism Research
Scientists have created the most detailed map to date of the human hypothalamus, a crucial brain region that regulates body weight, appetite, sleep, and stress.
HYPOMAP confirms the critical role of the hypothalamus in body-weight regulation and has already allowed us to identify new genes linked to obesityGiles YeoSander DalhuisenPerson holding burger bun with vegetables and meat
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