Dogs, like humans, are experiencing an obesity epidemic, with 40–60 percent of pet dogs classified as overweight or obese—a condition that increases their risk for various health issues.1 As pets share similar environmental influences as humans, researchers like Eleanor Raffan, a veterinarian and canine geneticist at the University of Cambridge, study animal genetics to find patterns that can apply to both pet and human health.
Obesity is a complex disease that results from genetic and environmental factors. Previously, Raffan and her team identified a gene mutation in Labradors associated with increased hunger and weight and lowered metabolism.2,3 However, Raffan wanted to dig deeper to find other genetic factors that might influence obesity in Labradors. In a new study published in Science, she and her team identified how a variation in the DENN domain containing 1B (DENND1B) gene put dogs at a higher risk for obesity.4 They found that this gene is shared by dogs and humans, so these findings offer valuable insights into canine eating behaviors and overall health.
To identify candidate obesity genes, Raffan and her team conducted a genome-wide association study for canine obesity in more than 200 adult Labrador retrievers. They identified five obesity-associated genes. Were these genes also relevant to human obesity?
To investigate, the team mapped the five candidate canine genes to their human counterparts and found a genetic association with human obesity. Among them, one variant in the DENND1B gene was the most strongly associated with body mass and obesity. Dogs with a mutation in this gene had about eight percent more body fat than those without it. Single-cell data from mice and humans revealed that DENND1B co-expressed with satiety signaling receptors like melanocortin 4 receptor (MC4R), a key regulator in energy balance, in the hypothalamus. In cell models, DENND1B overexpression interfered with MC4R signaling and increased appetite. Notably, the researchers also observed this signaling relationship in a patient with severe childhood obesity, whose DENND1B variant reduced MCR4 expression, likely contributing to their condition.
Based on these observations, the researchers developed a scoring system to predict obesity risk in dogs with this genetic trait. Taking their findings beyond the lab, the team surveyed dog owners to explore how a dog’s genetic profile and home interactions might affect its behavior. “We found that dogs at high genetic risk of obesity were more interested in food,” said Natalie Wallis, a molecular biologist at the University of Cambridge, in a press release. “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 [a] higher appetite, as has also been shown for people at high genetic risk of obesity.”
However, the team’s findings offer good news for pet owners: Strict owner control of diet and exercise kept high-risk dogs at a healthy weight. Meanwhile, Labradors with low genetic risk naturally maintained a normal weight.
“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,” said Raffan in a press release.
- German AJ, et al. Dangerous trends in pet obesity. Vet Rec. 2018;182(1):25.
- Raffan E, et al. A deletion in the canine POMC gene is associated with weight and appetite in obesity-prone labrador retriever dogs. Cell Metab. 2016;23(5):893-900.
- Dittmann MT, et al. Low resting metabolic rate and increased hunger due to β-MSH and β-endorphin deletion in a canine model. Sci Adv. 2024;10(10):eadj3823.
- Wallis NJ, et al. Canine genome-wide association study identifies DENND1B as an obesity gene in dogs and humans. Science. (2025);0:eads2145.
