A study in obese mice has found that the gut-derived hormone FGF19 can signal the brain to increase energy expenditure and activate fat-burning cells. Acting through the hypothalamus and the sympathetic nervous system, this mechanism enhances thermogenesis and cold tolerance and may help guide new treatments for obesity and diabetes.
Researchers at the State University of Campinas (UNICAMP) in Brazil report that the hormone FGF19 influences energy metabolism by acting on the hypothalamus, a brain region that coordinates responses to signals from the body and the environment.
In the study, diet-induced obese mice received FGF19 directly into the brain. According to the paper in the American Journal of Physiology – Endocrinology and Metabolism, central FGF19 signaling boosted sympathetic nervous system activity, increased energy expenditure and stimulated thermogenesis in brown and inguinal (white) adipose tissue, leading fat cells to burn energy as heat rather than store calories. The obese mice showed improved overall energy homeostasis, reduced peripheral inflammation, better glucose–insulin control and greater tolerance to cold exposure.
The work builds on earlier research showing that FGF19, produced mainly in the small intestine, regulates bile acids as well as glucose and lipid metabolism in the liver, while highlighting its less-explored effects in the brain. The authors found that exposure to cold upregulated receptors and coreceptors for FGF19 specifically in the hypothalamus, suggesting an adaptive role in thermoregulation and energy balance.
“FGF19 had already been linked to a reduction in food intake. Our work broke new ground by showing that it also plays an important role by acting on the hypothalamus and stimulating an increase in energy expenditure in white and brown adipose tissue. In other words, in addition to controlling appetite, it stimulates thermogenesis. So, in terms of therapy associated with obesity, it’d make a lot of sense,” said Professor Helena Cristina de Lima Barbosa, from the Obesity and Comorbidities Research Center (OCRC) at UNICAMP, in remarks reported by FAPESP.
The study, led by doctoral student Lucas Zangerolamo under Barbosa’s supervision, was funded by the São Paulo Research Foundation (FAPESP) and involved collaboration with the Joslin Diabetes Center at Harvard Medical School, where co-author Yu‑Hua Tseng is based. To map which brain cells could respond to FGF19, the team compiled and analyzed public single-cell RNA sequencing datasets from the adult mouse hypothalamus. They evaluated transcription in more than 50,000 individual cells to identify specific hypothalamic populations expressing FGF19 receptors.
The authors say a next step is to understand how to stimulate the body to increase its own production of FGF19 and to clarify how this pathway intersects with diet-induced brain inflammation and neural circuits that regulate eating behavior.
The findings come as obesity continues to rise worldwide. The World Atlas of Obesity 2025 estimates that more than 1 billion people are currently living with obesity and projects that, without stronger prevention and treatment measures, this number could exceed 1.5 billion by 2030.
The research, published in American Journal of Physiology – Endocrinology and Metabolism and highlighted by the journal earlier this year, suggests that drugs designed to mimic FGF19’s action in the brain and adipose tissue could one day complement existing hormone-based therapies for obesity and diabetes. Current medicines such as Ozempic, which contains semaglutide, work by activating GLP‑1 receptors to send satiety signals to the brain and reduce food intake; the new work points to FGF19 as a potential target for therapies that also directly increase energy expenditure.
