̽��ֱ�� of Cambridge - Wellcome-MRC Institute of Metabolic Science

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

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Map of brain’s appetite centre could enable new treatments for obesity and diabetes

Anonymous — Wed, 05 Feb 2025 16:00:15 +0000

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 type 2 diabetes.

̽��ֱ��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, ̽��ֱ�� 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. ̽��ֱ��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, type 2 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 obesity

Giles Yeo

Sander Dalhuisen

Person holding burger bun with vegetables and meat

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Genetic study points to oxytocin as possible treatment for obesity and postnatal depression

cjb250 — Tue, 02 Jul 2024 15:00:18 +0000

Obesity and postnatal depression are significant global health problems. Postnatal depression affects more than one in 10 women within a year of giving birth and is linked to an increased risk of suicide, which accounts for as many as one in five maternal deaths in high income countries. Meanwhile, obesity has more than doubled in adults since 1990 and quadrupled in adolescents, according to the World Health Organization.

While investigating two boys from different families with severe obesity, anxiety, autism, and behavioural problems triggered by sounds or smells, a team led by scientists at the ̽��ֱ�� of Cambridge, UK, and Baylor College of Medicine, Houston, USA, discovered that the boys were missing a single gene, known as TRPC5, which sits on the X chromosome.

Further investigation revealed that both boys inherited the gene deletion from their mothers, who were missing the gene on one of their X chromosomes. ̽��ֱ��mothers also had obesity, but in addition had experienced postnatal depression.

To test if it was the TRPC5 gene that was causing the problems in the boys and their mothers, the researchers turned to animal models, genetically-engineering mice with a defective version of the gene (Trpc5 in mice).

Male mice with this defective gene displayed the same problems as the boys, including weight gain, anxiety, a dislike of social interactions, and aggressive behaviour. Female mice displayed the same behaviours, but when they became mothers, they also displayed depressive behaviour and impaired maternal care. Interestingly, male mice and female mice who were not mothers but carried the mutation did not show depression-like behaviour.

Dr Yong Xu, Associate Director for Basic Sciences at the USDA/ARS Children’s Nutrition Research Center at Baylor College of Medicine, said: “What we saw in those mice was quite remarkable. They displayed very similar behaviours to those seen in people missing the TRPC5 gene, which in mothers included signs of depression and a difficulty caring for their babies. This shows us that this gene is causing these behaviours.”

TRPC5 is one of a family of genes that are involved in detecting sensory signals, such as heat, taste and touch. This particular gene acts on a pathway in the hypothalamus region of the brain, where it is known to control appetite.

When the researchers looked in more detail at this brain region, they discovered that TRPC5 acts on oxytocin neurons – nerve cells that produce the hormone oxytocin, often nicknamed the ‘love hormone’ because of its release in response to displays of affection, emotion and bonding.

Deleting the gene from these oxytocin neurons led to otherwise healthy mice showing similar signs of anxiety, overeating and impaired sociability, and, in the case of mothers, postnatal depression. Restoring the gene in these neurons reduced body weight and symptoms of anxiety and postnatal depression.

In addition to acting on oxytocin neurons, the team showed that TRPC5 also acts on so-called POMC neurons, which have been known for some time to play an important role in regulating weight. Children in whom the POMC gene is not working properly often have an insatiable appetite and gain weight from an early age.

Professor Sadaf Farooqi from the Institute of Metabolic Science at the ̽��ֱ�� of Cambridge said: “There's a reason why people lacking TRPC5 develop all of these conditions. We’ve known for a long time that the hypothalamus plays a key role in regulating ‘instinctive behaviours’ – which enable humans and animals to survive – such as looking for food, social interaction, the flight or fight response, and caring for their infants. Our work shows that TRPC5 acts on oxytocin neurons in the hypothalamus to play a critical role in regulating our instincts.”

While deletions of the TRPC5 gene are rare, an analysis of DNA samples from around 500,000 individuals in UK Biobank revealed 369 people – around three-quarters of whom were women – that carried variants of the gene and had a higher-than-average body mass index.

̽��ֱ��researchers say their findings suggests that restoring oxytocin could help treat people with missing or defective TRPC5 genes, and potentially mothers experiencing postnatal depression.

Professor Farooqi said: “While some genetic conditions such as TRPC5 deficiency are very rare, they teach us important lessons about how the body works. In this instance, we have made a breakthrough in understanding postnatal depression, a serious health problem about which very little is known despite many decades of research. And importantly, it may point to oxytocin as a possible treatment for some mothers with this condition.”

There is already evidence in animals that the oxytocin system is involved in both depression and in maternal care and there have been small trials into the use of oxytocin as a treatment. ̽��ֱ��team say their work provides direct proof of oxytocin’s role, which will be crucial in supporting bigger, multi-centre trials.

Professor Farooqi added: “This research reminds us that many behaviours which we assume are entirely under our control have a strong basis in biology, whether that’s our eating behaviour, anxiety or postnatal depression. We need to be more understanding and sympathetic towards people who suffer with these conditions.”

This work was supported by Wellcome, the National Institute for Health and Care Research (NIHR), NIHR Cambridge Biomedical Research Centre, Botnar Fondation and Bernard Wolfe Health Neuroscience Endowment.

Reference
Li, Y, Cacciottolo, TM & Yin, N. Loss of Transient Receptor Potential Channel 5 Causes Obesity and Postpartum Depression. Cell; 2 July 2024; DOI: 10.1016/j.cell.2024.06.001

Scientists have identified a gene which, when missing or impaired, can cause obesity, behavioural problems and, in mothers, postnatal depression. ̽��ֱ��discovery, reported on 2 July in Cell, may have wider implications for the treatment of postnatal depression, with a study in mice suggesting that oxytocin may alleviate symptoms.

This research reminds us that many behaviours which we assume are entirely under our control have a strong basis in biology. We need to be more understanding and sympathetic towards people who suffer with these conditions

Sadaf Farooqi

Olli Turho (Getty Images)

Illustration of a tired African American mother crying

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Exercising during pregnancy normalises eating behaviours in offspring from obese mice

Anonymous — Tue, 04 Jun 2024 18:00:43 +0000

Previous studies in both humans and animal models have shown that the offspring of mothers living with obesity have a higher risk of developing obesity and type 2 diabetes themselves when they grow up. While this relationship is likely to be the result of a complex relationship between genetics and environment, emerging evidence has implicated that maternal obesity in pregnancy can disrupt the baby’s hypothalamus—the region of the brain responsible for controlling food intake and energy regulation.

In animal models, offspring exposed to overnutrition during key periods of development eat more when they grow up, but little is known about the molecular mechanisms that lead to these changes in eating behaviour.

In a study published today in PLOS Biology, researchers from the Institute of Metabolic Science and the MRC Metabolic Diseases Unit at the ̽��ֱ�� of Cambridge found that mice born from obese mothers had higher levels of the microRNA miR-505-5p in their hypothalamus—from as early as the fetal stage into adulthood. ̽��ֱ��offspring of obese mothers chose to eat more specifically of foods that were high in fat, which is consistent with fat sensing being disrupted in the hypothalamus.

Dr Laura Dearden from the Institute of Metabolic Science, the study’s first author, said: “Our results show that obesity during pregnancy causes changes to the baby's brain that makes them eat more high fat food in adulthood and more likely to develop obesity.”

Senior author Professor Susan Ozanne from the MRC Metabolic Diseases Unit and Institute of Metabolic Science said: “Importantly, we showed that moderate exercise, without weight loss, during pregnancies complicated by obesity prevented the changes to the baby's brain.”

Cell culture experiments showed that miR-505-5p levels can be influenced by exposing hypothalamic neurons to long-chain fatty acids and insulin, which are both high in pregnancies complicated by obesity. ̽��ֱ��researchers identified miR-505-5p as a regulator of pathways involved in fatty acid uptake and metabolism – high levels of the miRNA make the offspring brain unable to sense when they are eating high fat foods. Several of the genes that miR-505-5p regulates are associated with high body mass index in human genetic studies, showing these same changes in humans can cause obesity.

̽��ֱ��study is one of the first to demonstrate the molecular mechanisms linking nutritional exposure in utero to eating behaviour.

Dr Dearden added: “While our work was only carried out in mice, it may help us understand why the children of mothers living with obesity are more likely to become obese themselves, with early life exposures, genetics and current environment all being contributing factors.”

Reference
Dearden, L et al. Maternal obesity increases hypothalamic miR-505-5p expression in mouse offspring leading to altered fatty acid sensing and increased intake of high-fat food. PLOS Biology; 4 Jun 2024; DOI: 10.1371/journal.pbio.3002641

Adapted from a press release by PLOS Biology

Maternal obesity in pregnancy changes the eating behaviours of offspring by increasing long-term levels of particular molecules known as microRNAs in the part of the brain that controls appetite – but this can be changed by exercise during pregnancy, a study in obese mice has suggested.

We showed that moderate exercise, without weight loss, during pregnancies complicated by obesity prevented the changes to the baby's brain

Susan Ozanne

Engin_Akyurt (Pixabay)

Fast food meal of burger and fries

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US Food and Drug Administration approves Cambridge-developed artificial pancreas

cjb250 — Fri, 24 May 2024 12:39:44 +0000

This means that even more people living with the disease will be able to use this life-changing app. For the first time, the FDA authorised the use of the artificial pancreas system in pregnancy.

CamAPS FX, produced by Cambridge spinout company CamDiab (www.camdiab.com), is an Android app that can be used to help manage glucose levels in people with type 1 diabetes, including during pregnancy.

̽��ֱ��app allows a compatible insulin pump and a compatible continuous glucose monitor to ‘talk to each other’, creating an artificial pancreas.

̽��ֱ��CamAPS FX closed loop algorithm was given FDA authorisation on Thursday 23 May. It had already been CE-marked for use in the UK and the EU.

CamAPS FX creator Roman Hovorka is Professor of Metabolic Technology at the Institute of Metabolic Science and Department of Paediatrics at the ̽��ֱ�� of Cambridge, where the technology was developed.

He said: "We set out to help people with type 1 diabetes and their families live better lives and we’re delighted that the FDA has reviewed the safety and effectiveness of CamAPS FX and has given the technology its approval."

"It has been extensively tested and we’re proud that it is considered by many to be the best algorithm out there."

CamAPS FX is already used by more than 27,000 people in 15 countries across Europe and Australia. Artificial pancreas systems such as CamAPS FX have been granted approval for wide use by the NHS in November 2023 by the National Institute for Health and Care Excellence (NICE).

Scientists identify rare gene variants that confer up to 6-fold increase in risk of obesity

Anonymous — Thu, 04 Apr 2024 12:36:17 +0000

̽��ֱ��discovery of rare variants in the genes BSN and APBA1 are some of the first obesity-related genes identified for which the increased risk of obesity is not observed until adulthood.

̽��ֱ��study, published in Nature Genetics, was led by researchers at the Medical Research Council (MRC) Epidemiology Unit and the MRC Metabolic Diseases Unit at the Institute of Metabolic Science, both based at the ̽��ֱ�� of Cambridge.

̽��ֱ��researchers used UK Biobank and other data to perform whole exome sequencing of body mass index (BMI) in over 500,000 individuals.

They found that genetic variants in the gene BSN, also known as Bassoon, can raise the risk of obesity as much as six times and was also associated with an increased risk of non-alcoholic fatty liver disease and of type 2 diabetes.

̽��ֱ��Bassoon gene variants were found to affect 1 in 6,500 adults, so could affect about 10,000 people in the UK.

̽��ֱ��brain’s role in obesity

Obesity is a major public health concern as it is a significant risk factor for other serious diseases, including cardiovascular disease and type 2 diabetes, yet the genetic reasons why some people are more prone to weight gain are incompletely understood.

Previous research has identified several obesity-associated gene variants conferring large effects from childhood, acting through the leptin-melanocortin pathway in the brain, which plays a key role in appetite regulation.

However, while both BSN and APBA1 encode proteins found in the brain, they are not currently known to be involved in the leptin-melanocortin pathway. In addition, unlike the obesity genes previously identified, variants in BSN and APBA1 are not associated with childhood obesity.

This has led the researchers to believe that they may have uncovered a new biological mechanism for obesity, different to those we already know for previously identified obesity gene variants.

Based on published research and laboratory studies they report in this paper, which indicate that BSN and APBA1 play a role in the transmission of signals between brain cells, the researchers suggest that age-related neurodegeneration could be affecting appetite control.

Professor John Perry, study author and an MRC Investigator at the ̽��ֱ�� of Cambridge, said: “These findings represent another example of the power of large-scale human population genetic studies to enhance our understanding of the biological basis of disease. ̽��ֱ��genetic variants we identify in BSN confer some of the largest effects on obesity, type 2 diabetes and fatty liver disease observed to date and highlight a new biological mechanism regulating appetite control.”

̽��ֱ��use of global data

̽��ֱ��accessibility of large-scale databases such as UK Biobank has enabled researchers to search for rare gene variants that may be responsible for conditions including obesity.

For this study, the researchers worked closely with AstraZeneca to replicate their findings in existing cohorts using genetic data from individuals from Pakistan and Mexico. This is important as the researchers can now apply their findings beyond individuals of European ancestry.

If the researchers can better understand the neural biology of obesity, it could present more potential drug targets to treat obesity in the future.

Dr Slavé Petrovski, VP of the Centre for Genomics Research at AstraZeneca, said: “Rigorous large-scale studies such as this are accelerating the pace at which we uncover new insights into human disease biology. By collaborating across academia and industry, leveraging global datasets for validation, and embedding a genomic approach to medicine more widely, we will continue to improve our understanding of disease – for the benefit of patients.”

Next steps for research

Professor Giles Yeo, study author based at the MRC Metabolic Diseases Unit, added: “We have identified two genes with variants that have the most profound impact on obesity risk at a population level we’ve ever seen, but perhaps more importantly, that the variation in Bassoon is linked to adult-onset and not childhood obesity. Thus these findings give us a new appreciation of the relationship between genetics, neurodevelopment and obesity.”

Reference
Zhao, T et al. Protein-truncating variants in BSN are associated with severe adult-onset obesity, type 2 diabetes and fatty liver disease. Nat Gen; 4 Apr 2024; DOI: 10.1038/s41588-024-01694-x

Adapted from a press release from the Medical Research Council

Cambridge researchers have identified genetic variants in two genes that have some of the largest impacts on obesity risk discovered to date.

We have identified two genes with variants that have the most profound impact on obesity risk at a population level we’ve ever seen

Giles Yeo

World Obesity Federation

Woman with obesity washing food

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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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Why seven in ten women experience pregnancy sickness

cjb250 — Wed, 13 Dec 2023 16:00:10 +0000

A Cambridge-led study has shown why many women experience nausea and vomiting during pregnancy – and why some women, including the Duchess of Cambridge, become so sick they need to be admitted to hospital.