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Diabetics’ Sugar Cravings May Have an On-Off Switch

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Diabetics’ Sugar Cravings May Have an On-Off Switch
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In a new study using mice models, researchers found that the fibroblast growth factor 21 (FGF21) hormone, produced by the liver, suppresses the urge to consume simple sugars. The research article, titled “FGF21 Mediates Endocrine Control of Simple Sugar Intake and Sweet Taste Preference by the Liver,” was published in the journal Cell Metabolism.

The liver is an organ of extreme importance in nutrient metabolism, and previous studies have shown that several hormones can regulate appetite. However, these hormones, also produced by the pancreas and other organs, have not yet been linked to specific nutrient intake regulation.

For the first time, researchers have identified a liver-derived factor called FGF21 that regulates nutrient preference and carbohydrate appetite. FGF21 has been previously shown to enhance insulin sensitivity, and previous genome-wide research studies identified associations between specific DNA mutations, two of these located in proximity to the FGF21 gene, and the consumption of specific nutrients. In light of these observations, researchers studied this hormone’s role in the regulation of nutrient preference.

The research team found that the liver regulates carbohydrate intake through the production of FGF21 hormone, which suppresses the consumption of simple sugars, but had no effect on the intake of other nutrients such as complex carbohydrates, proteins and lipids, and did not reduce the consumption of all sugars (sucrose, fructose, and glucose) equally. Using mice models, researchers observed that elimination of FGF21 increased sugar (sucrose) consumption and overproduction, and that acute administration of FGF21 via injection suppressed the consumption of both sugar and non-caloric sweeteners.

The results led the researchers to propose that FGF21 reduces sugar-seeking behavior and meal size through a negative feedback system between the liver and the brain, in which the liver increases the production of FGF21 as a response to sucrose ingestion.

“We’ve known for a while that FGF21 can enhance insulin sensitivity,” Lucas BonDurant, a doctoral student in molecular and cellular biology at the University of Iowa and the study’s co-first author, said in a press release. “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 researchers are now trying to identify the neuronal pathways involved in sugar consumption regulation and macronutrient preference, paying special attention to the hypothalamus, a region of the brain involved in regulating appetite and food consumption behavior. Co-senior author Dr. Matthew Potthoff said of the team’s future research, “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. If so, how do those signals intertwine to regulate the neural sensing of different macronutrients?”

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