Summary: Researchers report that people carrying a common FGF21 gene variant—sometimes called a “sweet tooth” variant—tend to have a lower total body-fat percentage, but that same variant is also associated with slightly higher blood pressure and a greater tendency toward abdominal (apple-shaped) fat distribution.
Source: University of Copenhagen
New research shows a common FGF21 gene variant linked to a sweet preference is also associated with lower total body fat but modestly higher blood pressure and increased waist-to-hip ratio.
Researchers at the University of Copenhagen and international collaborators have found that people who carry a specific variation in the FGF21 gene tend to consume more sugar and have a lower overall body-fat percentage than those without the variant. The finding builds on earlier work that connected this same genetic variation to a greater preference for sweets.
At first glance, the combination of higher sugar intake and lower body fat seems counterintuitive. “It may contradict the common expectation that people who eat more sugar accumulate more body fat,” says Associate Professor Niels Grarup from the Novo Nordisk Foundation Center for Basic Metabolic Research. “However, our study focuses specifically on this genetic variant and how it relates to multiple aspects of metabolism. This is one piece of a much larger puzzle linking diet, genetics, obesity and diabetes risk.”
Higher blood pressure and more abdominal fat
While the lower total body-fat percentage associated with the FGF21 variant might appear beneficial, the study also identified less favorable effects. Carriers of the variant showed a small but statistically significant increase in blood pressure and a higher waist-to-hip ratio—indicating a tendency toward an “apple-shaped” body with more fat around the waist relative to the hips.
The international study was led by researchers at the University of Exeter Medical School and published in Cell Reports. The conclusions draw on health and genetic data from more than 450,000 participants in the UK Biobank, including blood measurements, dietary questionnaires and genome information. The large sample size gives the findings considerable statistical robustness, even though the measured differences for body fat and blood pressure are modest.
“With such a large cohort, we can be confident that the associations we observe are real,” says Niels Grarup. “About one in five people of European ancestry carry this genetic predisposition.”
Implications for drug development
FGF21 is a hormone with insulin-sensitizing properties, and pharmaceutical research has explored FGF21 analogs as potential treatments for obesity and metabolic disease. Because the FGF21 variant affects macronutrient intake—particularly increasing carbohydrate and sugar consumption—understanding the consequences of that variation in humans helps predict possible benefits and side effects of therapies that target FGF21.
“FGF21 is an attractive target because of its links to sugar intake and metabolic regulation,” says Grarup. “Human genetic data like these provide important context for drug development, helping researchers anticipate unintended effects such as changes in blood pressure or body fat distribution.”
Funding: The study received support from multiple funders, including the European Research Council (ERC), the U.S. National Institutes of Health (NIH) and the Novo Nordisk Foundation.
Source: University of Copenhagen
Publisher: NeuroscienceNews.com (organized reporting)
Original research: The study, titled “A Common Allele in FGF21 Associated with Sugar Intake Is Associated with Body Shape, Lower Total Body-Fat Percentage, and Higher Blood Pressure,” was published in Cell Reports. The research used UK Biobank data to examine the effects of the A allele at rs838133 in FGF21 across 451,099 participants. DOI: 10.1016/j.celrep.2018.03.070
Fibroblast growth factor 21 (FGF21) influences metabolism and appetite, including macronutrient preferences. Previous studies found that a common human allele in FGF21 is linked to higher carbohydrate and alcohol intake, but metabolic consequences were unclear. In a sample of 451,099 UK Biobank participants, researchers replicated the association of the A allele (rs838133) with higher carbohydrate intake and demonstrated stronger associations with higher blood pressure and increased waist-to-hip ratio, despite an association with lower total body-fat percentage. These human phenotypes help inform understanding of FGF21’s mechanisms and the potential effects of therapies that target this hormone.
This research highlights how a single genetic variant can influence diet, body composition and cardiovascular traits in complex and sometimes opposing ways. The findings reinforce the importance of integrating genetic, dietary and metabolic data when considering therapeutic strategies that modulate hormonal pathways such as FGF21.