Blood glucose-lowering hormone FGF21 also activates brown adipose tissue metabolism

The blood glucose-lowering hormone FGF21 is also an activator of brown adipose tissue metabolism, according to the study featured on the cover of Cell Metabolism and directed by the lecturer Francesc Villarroya of the UB's Department of Biochemistry and Molecular Biology (Faculty of Biology),  the Institute of Biomedicine, and the Biomedical Research Networking Centre in Physiopathology of Obesity and Nutrition.

The study was carried out using newborn mice, and reveals possible new therapeutic targets for combating obesity using the fibroblast growth factor 21 (FGF21), which is secreted by the liver in response to fats in the diet. The team behind the research describe a novel action of FGF21 on brown adipose tissue, which governs energy expenditure and heat production in the body.

FGF21 is an antidiabetic and antiobesity agent that has been referred to in scientific literature since 2005", says Francesc Villarroya, an expert in the study of metabolism regulation models using genetically modified mice. He explains that, "Our study provides the first evidence that FGF21 causes thermogenesis in brown adipose tissue, that is, the burning of calories to release heat, dissipating large amounts of energy. Any agent that promotes and activates brown adipose tissue metabolism is, by definition, an antiobesity agent".

One of the major contributions of the study is the discovery of a direct link between FGF21 and brown adipose tissue. As Villaroya explains, "In in vivo studies we saw that the factor activates thermogenesis in brown adipose tissue. In the standard model, this process was regulated by the brain via an adrenergic pathway, but in new in vitro studies we have seen that the target of FGF21 was in fact not the brain but the brown adipose tissue. If FGF21 acts directly on brown adipose tissue and is independent of adrenergic control, we will have new ways of exploring mechanisms for controlling body fat".

The article examines the biological activity of EFG21 in a new model: newborn animals. "The work with newborn animal models is another crucial aspects of the study", says Villarroya, "We know that metabolic alterations during the foetal and neonatal stages have an impact on metabolism in the adult. In the case of mice, during the foetal stage they are fed by maternal glucose through the placenta. After birth, the mouse feeds on maternal milk rich in fats, which it must begin to metabolize. Therefore, newborn mice are excellent models for studying the process of adaptation to new metabolic demands".

Recent research carried out using positron emission tomography (PET) techniques had confirmed the high metabolic activity of brown adipose tissue in adults, a topic that had caused strong disagreements in the scientific community until now. Experts at the UB are currently developing new experimental protocols for gainer greater insight into the relationship between FGF21 and lipid metabolism, and the possible pharmacological or nutritional uses of this factor in weight control: "We know that the liver produces this factor in response to fatty acids in the diet, but not all fatty acids trigger the same response: the intensity of the signals and the liver response vary considerably. Could we modulate these signals using dietary strategies? Essentially, that would mean adapting diets in such a way that they induce greater production of FGF21, which would accelerate metabolism". They also believe that one of the major challenges over the coming years will be to determine the way in which this system works in obese or diabetic patients: "Unusually, it appears that obese adults produce larger quantities of FGF21, which would suggest that there is a problem of resistance that we have yet to uncover, and which will also need to be studied".