Bone morphogenetic protein 8B (BMP8B) plays a key role in regulating thermogenesis in brown adipose tissue, according to the findings of a research work published in Cell, the journal with the most impact on the field of biomedicine and molecular biology. The research group of Molecular Biology and Gene Regulation of the Adipose Tissue and its Diseases, led by Francesc Villarroya, professor at the Department of Biochemistry and Molecular Biology and director of the Institute of Biomedicine of the University of Barcelona (IBUB), affiliated centre to the campus of international excellence Barcelona Knowledge Campus (BKC) has taken part in the research.
The new research work, which presents a new mechanism to regulate brown adipose tissue, is also signed by experts from the Research Group of de NeurObesity (University of Santiago de Compostela), led by lecturer Miguel López, in collaboration with research teams from research centres in Iowa (United States), Stockholm (Sweden) and Cambridge (United Kingdom).
Brown adipose tissue: the mechanism for thermogenesis
One of the basic causes related to the epidemic of obesity is the malfunctioning of the brown adipose tissue. Unlike white adipose tissue, which is the most common type of fat, brown adipose tissue does not store up lipids. Instead, it oxidizes them in order to obtain energy which is released as heat. This phenomenon is known as thermogenesis. Hence, brown adipose tissue helps to "burn more calories" and to produce body heat from fat. For this reason, this special type of fat has attracted the attention of the research group as a potential therapeutic target to treat obesity. However, molecular mechanisms that regulate its functioning are not well known and further research is still needed.
Bone morphogenetic proteins are members of the transforming growth factor TGF-β family. Traditionally, they have been related to the formation of bone, cartilage and connective tissue. The results from the new study show that, for the first time, BMP8B is expressed in high levels in brown adipose tissue and in the hypothalamus, modulating key aspects of the thermogenesis.
As experts mention, knockout mice of BMP8B (that is, without the gene BMP8B) used for research, are markedly obese, despite having a reduced food intake, due to a lower capacity to burn fat in brown adipose tissue. The effects of BMP8B on brown adipose tissue are regulated by the hypothalamus, a very important brain area for the regulation of energy. The administration of minimum doses of BMP8B in the hypothalamus is sufficient to increase in a powerful way body temperature of animals, as a result of stimulating the production of heat by brown adipose tissue.
This action depends on the activity of the AMPK (AMP-activated protein kinase) in a small number of neurons in the hypothalamus, known as the ventromedial nucleus (VMH). Specifically, AMPK activation reverses the effect of BMP8B on the dissipation of heat by brown adipose tissue. The results obtained confirm the application of BMP8B and AMPK in the hypothalamus as potential therapeutic targets against obesity and to develop drugs as a control mechanism of the body mass.
An extensive multidisciplinary research
According to professor Francesc Villarroya, who is also a member of the CIBER Physiopathology of Obesity and Nutrition, "this has been an extensive multidisciplinary study which has required the participation of several research teams, under the coordination of Dr. Antonio Vidal-Puig from the University of Cambridge. The research team of the UB has contributed to the scientific work by determining the control mechanisms of gene expression resulting in the synthesis of this new regulator factor of thermogenesis in brown fat (BMP8B). In particular, we have seen that it is controlled by PPARα, a nuclear receptor previously known for its importance in controlling fat oxidation in the body. In fact, this is the receptor that is activated by drugs called fibrates, which are administered to patients with high triglyceride levels in the blood".
"For scientists -he goes on- it is very suggestive that this coordinated control exists between mechanisms of fat oxidation and of dissipation of calories in brown adipose tissue. This work encourages us to continue our research on the brown fat, a research line which has been developed for years with the objective of contributing to find ways to activate energy expenditure and prevent or treat the epidemic of obesity and diabetes which is increasingly taking place in our society".