The natural hormone unlocks a hidden key to burning fat

Researchers linked these effects to the action of FGF19 in the hypothalamus, a key area of ​​the brain that receives information from the rest of the body and the environment to coordinate energy metabolism. They found that when FGF19 sends signals in the hypothalamus, it enhances the activity of thermogenic adipocytes (i.e., fat cells that burn energy to produce heat), which are specialized fat cells that help the body generate heat rather than store calories.

New paths to treat obesity and diabetes

Because of these findings, scientists believe that FGF19 could inspire new drugs for obesity, diabetes and other metabolic conditions. The idea is to develop compounds that mimic the behavior of natural substances in the body, and to mimic the action of endogenous compounds (i.e. those produced by the body itself).

This strategy is similar to the way some of the newer diabetes and obesity drugs work. For example, Ozempic contains semaglutide, an ingredient that activates receptors that mimic the hormone GLP-1. By doing this, it sends satiety signals to the brain and helps patients feel full with less food.

According to the study, FGF19 did more than just change appetite or fat storage. This hormone also reduced peripheral inflammation and improved the animals’ ability to tolerate cold. But when the researchers turned off the sympathetic nervous system, these benefits disappeared. In other experiments, they observed that exposure to cold increased the expression of FGF19 receptors in the hypothalamus. Because the hypothalamus is essential for maintaining body temperature, these findings suggest that FGF19 may help the body adapt by coordinating energy balance and thermoregulation.

FGF19, thermogenesis, and brain control of energy

“FGF19 has already been linked to decreased food intake. Our work has broken new ground by showing that it also plays an important role by acting on the hypothalamus and stimulating increased energy expenditure in white and brown adipose tissue. In other words, in addition to controlling appetite, it stimulates thermogenesis. Therefore, in terms of treatment related to obesity, it would make a lot of sense,” explains Professor Helena Cristina de Lima Barbosa, from the Department of Obesity and Comorbidities. Research Center (OCRC) at the State University of Campinas (UNICAMP).

OCRC is a Research, Innovation and Dissemination Center (RIDC) of FAPESP, which also funded the project through grants to doctoral student Lucas Zangirolamo, first author of the study, which Barbosa supervised.

The work is described in detail in an article published in the American Journal of Physiology-Endocrinology & Metabolism, where it was highlighted as a lead article in May.

The global obesity crisis and urgent health goals

The Global Obesity Atlas 2025 warns that if current trends continue, this year’s global health goals will not be met. These goals include halting rising rates of diabetes and obesity, and reducing premature deaths from cardiovascular disease, chronic respiratory disease, and cancer by 25%, using 2010 as the reference year.

The atlas estimates that more than one billion people worldwide currently suffer from obesity. If effective action is not taken, this number could exceed 1.5 billion by 2030. Obesity is already linked to about 1.6 million premature deaths each year from non-communicable diseases.

In Brazil, about 31% of the population suffers from obesity. In addition, 40% to 50% of adults do not reach recommended levels of physical activity in terms of frequency or intensity.

Where does FGF19 come from and how does it work

FGF19, which is involved in the control of energy metabolism, is produced mainly in the small intestine. In the liver, it regulates the production of bile acids and also affects the synthesis of glucose and lipids. While its essential roles in the liver have been extensively explored in the scientific literature, its effects in the brain have received much less attention.

“In the laboratory, we work with bile acids, which are also the subject of our master’s degree, and they regulate the release of FGF-19. Our initial studies led us down this path,” Zangirolamo told FAPESP.

At eight weeks old, the mice used in the study were randomly divided into two groups. One group received a standard diet (control) and the other group was fed a high-fat diet to induce obesity. The researchers then introduced FGF19 directly into the brains of obese animals. All mice were kept under carefully controlled conditions in terms of temperature, lighting, and access to water.

In the article, the scientists report that central FGF19 signaling improves energy balance. It does this by enhancing sympathetic nervous system activity and stimulating thermogenesis in adipose tissue, causing the tissue to consume more energy in the form of heat.

“The brain plays a very important role in controlling body fatness,” Barbosa adds. “At the same time as it receives information from peripheral tissues, it issues commands. These commands, which apparently use the sympathetic nervous system, are an interesting way to think about energy expenditure.”

Digging deeper into brain cells and FGF19 receptors

To better understand which brain cells respond to FGF19, the researchers pooled and examined public scRNA-seq data from several studies of the hypothalamus. This method allows RNA to be sequenced from individual cells, revealing which genes are active in each cell type. In total, the team evaluated transcriptomes from more than 50,000 single cells to identify groups of hypothalamic cells that express FGF19 receptors.

The main question now is how to encourage the body to produce more FGF19 on its own, the researchers point out. They are also working to connect these findings to what is already known about the neural circuits that regulate eating behavior.

“We want to expand this understanding,” says Zangirolamo, who did part of the work during his internship at the Joslin Diabetes Center at Harvard Medical School with Professor Yu-Hua Tseng, who is also the author of the article. “We are studying the hypothalamus to evaluate the inflammation commonly observed with a high-fat diet and whether FGF19 plays a role in this area.”