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Diet and lifestyle

Sugar mystery: gene variant is associated with increased sugar intake but a lower body-fat percentage

Danish researchers recently published a study showing that a variation in a gene can increase the craving to eat more sugar. The researchers hoped that this would turn out to be a way to treat obesity and diabetes. Now the same researchers have shown that the same gene variant that is associated with eating more sugar is also associated with a lower body-fat percentage. The results have sent researchers back to the drawing board in developing new medicine to treat obesity.

New knowledge on healthy and unhealthy diets can help us to lead a healthier life. However, such new knowledge often confuses both researchers and consumers. A good example of this is recent research on fibroblast growth factor 21 (FGF21), a hormone. A recent study showed that people with a specific variation in the FGF21 gene were 20% more likely to consume large quantities of candy and other food containing sugar. Intuitively, one would therefore think that these people would be more likely to become overweight, but this was not the case.

“We saw no correlation with being overweight. Although these people tend to eat more sugar, they actually had a lower body-fat percentage. This contradicts the current perception that eating sugar is bad for a person’s health, but it may arise because the same genetic variant also results in these people generally eating less fat. The new knowledge is important to show the complex relationship between what we eat and obesity” explains Niels Grarup, Associate Professor, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen.

Genetic variation redistributes fat

The new results are based on an especially thorough study. This compared the alleles for the FGF21 gene of more than 450,000 people from UK Biobank with such physical characteristics as weight, waist circumference, blood pressure and the presence of such diseases as diabetes. The researchers had thought that using this method would enable them to identify the variation in this gene that triggers obesity and diabetes.

“We were really surprised that the version of the gene that was associated with people eating more sugar is actually associated with a lower body-fat percentage. However, we cannot conclude that eating sugar is not unhealthy. The body-fat percentage may well be low for other reasons, and the genetic variant tends to redistribute fat to the torso, where it can cause more damage.”

One effect associated with the redistribution of fat is elevated blood pressure. However, this increase should not concern people unduly, since this was equivalent to an increase in systolic blood pressure from 120.00 to 120.33. Nevertheless, the redistribution of fat may be a cause for concern because experience shows that fat around the organs is much more dangerous than fat under the skin.

“One limitation of this type of study is that we cannot show which mechanisms make FGF21 change the quantity and distribution of body fat. This is what future research must show. At present, the only thing we can say for certain is that the genetic variation is associated with an increased craving for sugar, redistributed fat and a lower body-fat percentage.”

More knowledge required

FGF21 is secreted by the liver and transported by the bloodstream to the hypothalamus in the brain, where it helps to regulate the craving for sugar. However, this hormone has several functions, including influencing the uptake of glucose in fat cells and insulin sensitivity.

“Note how many processes FGF21 regulates in the body, and these are also affected if the amount of FGF21 increases. Similarly, many other signals play a role in regulating appetite, fat storage and metabolism.”

Trials on people are already underway, in which researchers are investigating whether FGF21 can be used regulate carbohydrate metabolism. Naturally, the hope is to minimize the risk of developing obesity and diabetes. These trials will perhaps be re-evaluated based on this latest study.

“FGF21 undoubtedly plays a key role in our health, but the new study once again shows that more knowledge is required. We need to understand the potential benefits and unintended side-effects of manipulating with this hormone before we can develop an effective treatment.”

A common allele in FGF21 associated with sugar intake is associated with altered body shape, lower total body-fat percentage, and higher blood pressure” has been published in Cell Reports. Niels Grarup, Associate Professor, is employed at the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen.

Niels Grarup
Associate Professor
Type 2 diabetes is a disorder caused by a subtle combination of heritable factors and environmental and lifestyle risk factors. Also intermediary diabetes-related physiological traits such as obesity, insulin resistance and disturbed insulin secretion have been shown to be partly modulated by genetic factors. My research interests are focused on identification genetic variation associated with type 2 diabetes (diabetes genomics discovery) and on performing detailed physiological characterization of these variants in relation to diabetes phenotype (genetic-epidemiology and genetic-physiology studies). Genetic variation is explored by both next generation nucleotide sequencing and by large-scale genotyping array-based genotyping. The long term goals are to gain a deeper understanding of the genetic architecture of type 2 diabetes, to expand our insights into diabetes pathogenesis and pathophysiology and possibly thereby derive novel drug targets for diabetes and in the longer term cause advances in clinical diabetes management and prevention.