International Business Department           Liu Bojia           March 11, 2025

  When talking about animal experimentation, the first subject most people associate with is the mouse, and some readers may also think of nematodes or zebrafish. These animals are common model animals in many studies. But in fact, as one of the pets of human beings, dogs also have an important position in biology and medical research, for example, the ‘Pavlov's dog’ experiment is a classic experiment to study the conditioned reflex. For example, the ‘Pavlov's Dog’ experiment is a classic experiment to study conditioned reflexes. Many studies involving the cardiovascular system and endocrine system also often choose dogs as research subjects.

  Compared to mice, the dog genome is more similar to the human genome, and dogs share a large number of living environments with humans, so they can more realistically reflect the changes in various physiological conditions. And today, Labradors are featured in the journal Science with the latest research data. Yes, you heard that right - the Labradors that many people keep in their homes.

  A team of researchers led by the University of Cambridge has revealed in depth the genetic mechanisms of obesity in Labradors, and they found that the gene called DENND1B is strongly associated with obesity in dogs, and that variants in DENND1B may also elevate the risk of obesity in humans. In addition, the researchers found that even though dogs carry unfavourable genetic conditions, they can be prevented from developing obesity with strict dietary control and increased exercise, which sheds a whole new light on obesity prevention and treatment in humans.

  For the study, the authors first assessed the body fat percentage and obesity level of 241 Labradors and collected their DNA samples. The study then analysed the genetic variants that have a high correlation with obesity with the help of genome-wide association analysis (GWAS) technology. The results showed that DENND1B gene variants were strongly associated with obesity in dogs. Compared to dogs that did not carry any DENND1B gene variants, the body fat percentage increased by about 7 per cent in carrier individuals. This means that if a Labrador has a mutated version of this gene, it may be more prone to obesity.

  The study found that the DENND1B protein is an important regulator of energy homeostasis, acting by affecting the pathway between leptin and the melanocortin 4 receptor (MC4R), which is itself an important ‘switch’ in the brain for controlling appetite and energy expenditure, and that the specific variant in DENND1B affects endocytosis and signalling in the MC4R. The specific variant of DENND1B affects the endocytosis and signalling of MC4R, which in turn affects the eating behaviour and body fat storage status of Labrador dogs. Academic Meridian has also previously reported on the regulatory mechanisms of MC4R and appetite: for example, when individuals enter middle age, MC4R receptors on the surface of hypothalamic neurons gradually decrease, reducing satiety signals.

  In addition to the DENND1B gene, the analyses also suggest that another gene, called POMC, is also linked to obesity. Normally, the protein encoded by the POMC gene is cleaved in the body into a variety of neuropeptides that play an important role in regulating appetite and energy expenditure. The study found that about 25 per cent of Labradors carry a mutated version of the POMC gene, a mutation that causes dogs to be more likely to feel hungry and consume less energy, and thus be more likely to gain weight.

  Notably, the study, which analysed genomic data from over 800,000 people, found that DENND1B gene variants were significantly associated with body mass index (BMI) in humans. Some rare DENND1B gene variants are associated with severe childhood obesity, which also disrupts energy balance by affecting MC4R-related signalling pathways.

  Unsurprisingly, environmental factors also play an important role in obesity in dogs, and can even overcome the influence of genes. In the case of domesticated Labradors, the way their owners raise them determines their level of obesity. The study categorised different dogs with the help of a polygenic risk score, with dogs with higher scores generally representing dogs that carry more obesity risk gene traits and are more prone to obesity. Behaviourally, dogs with high scores liked to explore the house for food and to ask their owners for treats.

  However, if owners strictly limit what they feed their dogs and increase exercise training, they can avoid gaining weight even if they carry unfavourable genetic factors. In contrast, dogs with lower genetic risk were less likely to gain weight, even if their owners managed their diet and exercise very loosely.

  The researchers note that this study not only has important implications for maintaining the health of dogs, but also provides a new perspective on obesity research in humans. By comparing the genes of Labradors and humans, scientists are able to better understand the genetic mechanisms of obesity. In addition, the study highlights the complex relationship between genes and the environment. For humans, this means that even if we have a higher genetic risk for obesity, we can still expect to maintain a healthy weight as long as we adhere to a healthy lifestyle and dietary management.