Brown adipose tissue — main organ generating heat in the body- is also an endocrine organ that secretes signaling factors that activate the fat and carbohydrates metabolism.
Key Points
- The activity of brown adipose tissue (BAT) is associated with protection against obesity and associated metabolic alterations such as insulin resistance
- Experimental evidence indicates that BAT has systemic effects by secreting regulatory molecules in addition to its capacity to use metabolic substrates for thermogenesis
- Brown and beige adipocytes secrete multiple autocrine and paracrine factors that control expansion and activity of BAT and the extent of browning of white adipose tissue
- BAT releases endocrine factors that can target peripheral tissues such as white adipose tissue, liver, pancreas, heart and bone, as well as affect systemic metabolism by interacting with the CNS
This is the main conclusion of an article published in Nature Reviews Endocrinology, signed by the professors Francesc Villarroya, Rubén Cereijo, Joan Villarroya and Marta Giralt, from the Department of Biochemistry and Molecular Biology of the University of Barcelona and CIBER of Physiopathology in Obesity and Nutrition (CIBERobn) of the Institute of Health Carlos III.
Brown adipose tissue: More than burning calories in the body
Brown adipose tissue (BAT) helps “burn more calories” and make body heat out of fat. According to the new study, this special kind of fat -the motor of thermogenesis- has an endocrine function able to activate the lipid and glucidic metabolism in the body, which has a profile for a future therapeutic target to treat pathologies like obesity.
“Traditionally, brown adipose tissue was just seen as an organ to burn calories, but we have seen it has an endocrine biological role,” said Professor Francesc Villarroya, member of the Institute of Biomedicine of the University of Barcelona (IBUB) and head of the Research Group in Genetics and Molecular Biology of Mitochondrial Proteins and Associated Diseases.
New perspectives in the physiology of brown adipose tissue
This new vision on the brown adipose tissue means a revolution similar to the one from years ago with white adipose tissue (WAT), the most known fat. “Until the eighties -says Villarroya- people believed WAT was a mere fat storage. From the nineties on, after discovering leptin as a hormonal factor released by WAT, other adipokines were found (active factors synthesized by this organ).” Therefore, WAT is now understood as an endocrine organ and now, with BAT, the same process is going on.
According to the experts, when there is a situation of BAT activation and there is a high oxidation in metabolism products to generate heat, this organ would also send a series of biochemical signals to the entire organism to activate the global oxidizing metabolism. Identifying the released factors -called batokines– is the main challenge of the researchers, apart from discovering how the target organs act, or if there are other secretory tissues, etc.
The most known factors are FGF21 (fibroblast growth factor 21), neuregulin 4 and IL-6, among other compounds that are the focus of an intense research activity. “White adipose tissue, liver, heart, and probably pancreas and brain (counting the regulation points of feelings of hunger and thirst) are some of the target organs of the batokines,” says Villarroya. “We also know that some of the factors released by WAT, such as FGF21, are able to cross the blood-brain barrier and act on brain areas” he said.
From basic research to human physiology
BAT secretory function as an endocrine organ has been studied through laboratory animal models and in vitro cell culture.
In studies with animal models, there were improvements in the diabetes course -and even obesity- in mice transferred with small samples of brown adipose tissue. According to the experts, the transferred BAT would release factors that promote glucose uptake and sensitivity to insulin (in general, a healthier metabolic profile).
“In human physiology -says Villarroya- it is essential to define if all batokines that are identified in animal models are also present in human BAT and behave the same way. In a future, these batokines could be considered as potential candidates in drug design to treat these diseases. In the case of obese patients with few active BAT -and probably less released batokines- a first therapeutic strategy could be to give them these molecules as drugs.”
However, moving this basic research to the clinical field is a hard challenge, for several reasons but also for the hard availability of samples through human biopsies. For this reason, among other strategies, the team of Dr. Villarroya is developing in vitro human cells of brown adipose humans in population that allow verifying in human physiology the obtained results in mice.
Journal Reference: Francesc Villarroya, Rubén Cereijo, Joan Villarroya, Marta Giralt.Brown adipose tissue as a secretory organ.Nature Reviews Endocrinology, 2016; DOI:10.1038/nrendo.2016.136