Sugar cravings are common but the physiological mechanisms that trigger a sweet tooth have not, until now, been well defined.
A new study with mice shows that a hormone produced by the liver, fibroblast growth factor 21 (FGF21), suppresses the consumption of simple sugars. The hormone is produced in response to high carbohydrate levels and then enters the bloodstream, where it sends a signal to the brain to suppress the preference for sweets.
“This is the first liver-derived hormone we know that regulates sugar intake specifically,” says Matthew Potthoff, assistant professor of pharmacology at the University of Iowa.
Previous research explains how certain hormones affect appetite; however, these hormones do not regulate any specific macronutrient (carbohydrate, protein, fat) and are produced by organs other than the liver.
The findings could improve diets and help patients who are diabetic or obese.
“We’ve known for a while that FGF21 can enhance insulin sensitivity,” says Lucas BonDurant, a doctoral student in molecular and cellular biology. “Now, there’s this dimension where FGF21 can help people who might not be able to sense when they’ve had enough sugar, which may contribute to diabetes.”
The new work, published in the journal Cell Metabolism, is based on human genome-wide studies where researchers found associations between certain DNA mutations and a person’s intake of specific macronutrients. Two of these mutations were located near the FGF21 gene, prompting researchers to identify the role of this hormone in regulating macronutrient preference.
They used genetically engineered mouse models and pharmacological approaches to examine the role of FGF21 in regulating sugar cravings. Normal mice were injected with FGF21 and given choice between a normal diet and a sugar-enriched diet. Researchers observed that the mice didn’t completely stop eating sugar, but ate seven times less than usual.
The researchers also studied genetically modified mice that either didn’t produce FGF21 at all or produced a lot of FGF21 (over 500 times more than normal mice). The modified mice had a choice between the same two diets as the normal mice. The mice that didn’t produce FGF21 at all ate more sugar, while the mice that produced a lot of FGF21 ate less.
Based on these results, the team concluded that FGF21 decreases appetite and intake of sugar. However, FGF21 does not reduce intake of all sugars (sucrose, fructose, and glucose) equally. FGF21 also doesn’t affect the intake of complex carbohydrates.
While the researchers discovered that FGF21 sends signals to the brain, additional work is necessary to identify the neural pathways that regulate FGF21’s ability to manage macronutrient preference. They are now focused on the hypothalamus—a section of the brain responsible for regulating feeding behavior and energy homeostasis.
“In addition to identifying these neural pathways, we would like to see if additional hormones exist to regulate appetite for specific macronutrients like fat and protein, comparable to the effects of FGF21 on carbohydrate intake,” Potthoff says.
“If so, how do those signals intertwine to regulate the neural sensing of different macronutrients?”
Other researchers from the University of Iowa, the University of Copenhagen, and the University of Colorado School of Medicine are coauthors of the study.
The American Diabetes Association, the National Institutes of Health, the Edward Mallinckrodt Jr. Foundation, the University of Iowa Fraternal Order of Eagles Diabetes Research Center, and the Novo Nordisk Foundation Center for Basic Metabolic Research funded the work.
Source: University of Iowa