AsianScientist (Mar. 3, 2016) – The unfolded protein response has been shown to link up with brown fat tissue to burn fat more effectively. These findings, published in Scientific Reports, may provide some clues to establishing control over obesity and diabetes.
Fat cells are classified as either brown or white. White fat accumulates during unhealthy weight gain, whereas brown fat is essential for a healthy metabolism. Uncoupled protein 1 (UCP1) is found abundantly in the mitochondria of brown fat cells and helps warm-blooded animals maintain a stable internal body temperature. This process, called thermogenesis, involves burning excess energy inside the body rather than storing it as fat. More UCP1 means a higher metabolism and less weight gain.
All cells are equipped with the unfolded protein response, a protective mechanism that prevents damage and cell death caused by the accumulation of wrongly folded proteins called endoplasmic reticulum (ER) stress. Although overactivation of the unfolded protein response has been linked to diseases such as Alzheimer’s and Parkinson’s, there is evidence that it also plays a positive role by interacting with other regulatory pathways.
In the present study, researchers led by Professor Kazunori Imaizumi from Hiroshima University studied mouse fat cells to investigate the relationship between UCP1 and the unfolded protein response. They found that increasing the levels of UCP1 activated the branch of the unfolded protein response involving the proteins IRE1alpha and XBP1.
Conversely, the activation of the unfolded protein response by endoplasmic stress did not affect the levels of UCP1. However, if the unfolded protein response proteins IRE1alpha and XBP1 were activated by an alternative pathway involving another protein known as PKA, UCP1 levels were increased.
These results provide strong evidence that the unfolded protein response is possibly one way fat cells maintain precise control of metabolic process using UCP1.
Current treatments for metabolic diseases like Type 2 diabetes and obesity rely on reducing the amount of energy entering the cells. These treatments focus on reducing white fat cells, which store excess calories. Treatments targeting UCP1, however, would work by increasing the amount of energy leaving the body. This would require the seemingly counter-intuitive method of increasing the number of brown fat cells.
“Brown fat cells dissipate excess energy in the form of heat. Therefore, having a large number of brown fat cells leads to an anti-obesity effect,” said study first author Rie Asada, a postdoctoral fellow in Imaizumi’s lab.
The research team is currently planning experiments to develop a more detailed understanding of the cellular pathways that lead to UCP1’s metabolic actions within brown fat cells.
The article can be found at: Asada et al. (2015) IRE1α-XBP1 is a Novel Branch in the Transcriptional Regulation of Ucp1 in Brown Adipocytes.
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Source: Hiroshima University; Photo: Shutterstock.
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