Brown adipose tissue, brown fat, is a key tissue that controls the energy balance of whole body. Excessive energy is dissipated in the form of heat by brown adipocytes specialized for thermogenesis or heat generation. Brown fat plays important roles in protecting neonates and small mammals, such as mice, against cold.
As the energy consumption system in brown fat is attractive for counteracting obesity and its related metabolic diseases, it is important to understand its mechanisms and modes of action. Now, a study from researchers at Hiroshima University has mapped the activation pathway for a protein, only found in brown fat, responsible for burning excess energy in the body. The team state that if the pathway can be confirmed in preclinical studies, control of this pathway may lead to treatments for obesity and related metabolic diseases. The opensource study is published in the journal Scientific Reports.
Previous studies show that the unique metabolic properties of brown fat result from its densely packed mitochondria containing uncoupling protein 1 (UCP1) in their inner membrane. Studies show that UCP1 is almost exclusively expressed in brown fat and is involved in the process of how warm-blooded animals maintain a stable internal body temperature. This process, thermogenesis, involves burning excess energy inside the body rather than storing it as fat, so more UCP1 means a higher metabolism and less weight gain. The current study investigated two proteins called IRE1alpha and XBP1 for their relationship to UCP1.
The current study utilised mouse fat cells growing in a dish using a combination of chemical treatments and protein measurements. Results show when the IRE1alpha and XBP1 proteins are active, they can increase the amount of UCP1 inside the cell. Data findings also identified other molecules that act even earlier in the control pathway.
Results identify a physiological role of unfolded protein response in BAT, with the IRE1α-XBP1 pathway activated during the transcriptional induction of UCP1. The group state that these findings provide strong evidence that somewhere within this cellular signaling cascade is the possibility for precision control of fat cells’ metabolic process using UCP1.
The team surmise that current treatments for metabolic diseases like type 2 diabetes and obesity rely on reducing the amount of energy entering the cells, however, treatments targeting UCP1 would be completely novel by increasing the amount of energy leaving the body. They go on to add that this would require the seemingly counter-intuitive method of increasing the number of brown fat cells. For the future, the researchers are planning experiments to develop a more detailed understanding of the cellular pathways that lead to UCP1’s metabolic actions within brown fat cells.
Source: Hiroshima University
