Some dogs, like Labrador retrievers, are prone to obesity. Scientists have investigated the genetics of British Labrador retrievers and found several obesity-linked genes that were then also associated with human obesity. This work showed that a gene called DENND1B has a strong link to Labrador obesity. Humans carry a version of the DENND1B gene, and the investigators revealed that it was also linked to human obesity. The findings have been reported in Science.
For this study, the investigators recruited volunteers who owned pet dogs. The researchers took measurements from the dogs: of body fat; a saliva sample for DNA; and a greediness assessment. When the genetic data was compared to the physicality of the dogs, the researchers found the genes that were associated with obesity. There are small variations in the sequences of the genes that predispose certain dogs to obesity. The variant that was most strongly associated with obesity was in DENND1B, and dogs with this variant had about 8% more body fat compared to dogs that did not carry this variant.
The scientists followed up on these results with human genetic data, including large cohorts that contained sequencing data from individuals with early onset, severe obesity. Variants in DENND1B also increased the likelihood of both rare and common forms of human obesity caused by genetics.
Additional work revealed that DENND1B can directly affect a crucial pathway in the brain related to human metabolism, which is known as the leptin melanocortin pathway. The work highlights the importance of fundamental pathways that help control appetite and body weight, noted co-first study author Alyce McClellan of the University of Cambridge.
Since the gene relates to a critical pathway, it is not likely to be a good drug candidate.
There were also other obesity-linked variants identified in dogs, which had a smaller effect than DENND1B, but were also relevant to humans. There was no single genetic variant that made a dog obese, but the effect of multiple genetic variants could have a strong impact.
“We found that dogs at high genetic risk of obesity were more interested in food,” said co-first study author Natalie Wallis, also of the University of Cambridge. “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 also determined that when pet owners maintained strict control over their dogs' diet and exercise, dogs with a high genetic predisposition to obesity could be kept at a healthy weight. A lot of effort was needed, however.
People who are carriers of variants that predispose them to obesity won't become obese for sure, but they also have to strictly control their diet and make exercise a habit.
“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 senior study author Dr Eleanor Raffan, also of the University of Cambridge.
Sources: Cambridge University, Science
