Last year, scientists at the University of Copenhagen discovered that people who have a particular variation in the gene FGF21 tend to crave sweet foods. Now new research from the same group has turned up a surprising finding: The same genetic variation is found in people who naturally have low body fat.
This doesn’t mean that everyone with a sweet tooth should feel free to load up on candy bars, however. “This is just a small piece of the puzzle describing the connection between diet and sugar intake and the risk of obesity and diabetes,” said Niels Grarup, associate professor at the university and a member of the Novo Nordisk Foundation Center for Basic Metabolic Research, in a statement. Novo Nordisk’s organization was one of the funders of the study.
The researchers made the FGF21 discovery using health information from 450,000 people whose genomes have been sequenced by UK Biobank, which also regularly collects information from its participants on diet, digestive health and other factors. The genetic variation was associated not only with high sugar intake, but also with the propensity to drink more alcohol and eat low-protein, low-fat diets. They published their findings in the journal Cell Reports.
But the variant they focused on isn’t all positive in its impact on body size. People who have it are also more prone to develop high blood pressure and to store more of their fat around their waists, not their hips, the team reported.
Where the findings could prove useful is in drug development, Grarup believes. Researchers have been investigating FGF21 as a target for drugs to treat obesity or diabetes. The protein made by the gene, fibroblast growth factor 21, has been shown to improve insulin resistance and fat metabolism. But Grarup’s study found no antidiabetic properties associated with the FGF21 variant that his group studied, according to the paper. And despite the variant’s association with lower body fat, it didn’t seem to have a strong link to body mass index, the most popular measure for determining whether someone is obese.
The search for a gene-based cure for obesity continues at labs around the world. Last year, a team at Washington University in St. Louis found that mice engineered with genes to activate the hedgehog signaling pathway in fat cells did not become obese, even when fed a high-fat diet. The researchers discovered that stimulating the pathway kept fat cells from expanding in size. Rhythm Pharmaceuticals, which is developing two drugs to treat rare genetic diseases that cause obesity, raised $120 million in an oversubscribed IPO last fall.
The University of Copenhagen researchers acknowledge that there is still much to be learned about variants of FGF21 and how they impact metabolic disorders. Because the study was based on information volunteered by participants in the UK Biobank, they could not prove a direct link between the gene variant and altered FGF21 expression, they noted in their study. Still, they argued, the association between the variant and the traits they observed “provide further insight into the potential multiple metabolic effects of FGF21” and could spark hypotheses that lead to new therapies targeting the gene.