A new approach to obesity could be on the horizon, say scientists from the University of Pennsylvania, who believe they have found the secret for turning white fat into brown fat. Their findings are published online in the journal Genes and Development.
Fat is not just fat. The human body has different types of fat, and they fulfill different purposes.
White fat cells, also known as white adipocytes, store fat. They are filled with fat molecules. If they contain too much fat, a person becomes obese.
Brown fat, on the other hand, is sometimes called “good” fat. Brown fat cells, or brown adipocytes, form the “baby fat” seen in infants.
Obesity and related conditions are considered largely preventable. Lifestyle changes are recommended for reducing obesity. However, in severe cases, people may undergo surgery.
Now, researchers have found a signaling pathway that can activate “browning” in white fat cells, making them more likely to burn fat, like brown fat cells.
Senior author Dr. Zoltan P. Arany and colleagues, from Penn University, carried out an experiment in which they deleted a gene in the white fat cells of mice. The gene, or protein, is known as foliculin (FLCN). FLCN has been identified as a tumor suppressor.
Once this gene was deleted, a protein known as TFE3 was able to enter the nucleus of the cells.
There, the scientists found that TFE3 would bind to DNA. In doing so, it activated a protein known as PGC-1β. PGC-1β plays a key role in regulating cell metabolism.
This process switched on a set of genes that turned the white fat “brown.”
Normally, this process does not occur, because the TFE3 protein cannot enter the cell nucleus. Two other genes – known as FCLN and mTOR – work together to keep it out; mTOR is a major signaling hub in cells.
This collaboration keeps the browning process switched off.
When the scientists deleted FLCN in the mice, they noticed that the white cells became browner.
One reason why this happened was that the cells started producing more mitochondria – the minuscule oxygen reactors that provide chemical energy inside cells. In brown fat cells, the mitochondria convert energy into heat.
The white fat cells became more like brown cells in other ways, too.
Deleting the gene changed the structures of the cells, it boosted the mitochondria’s ability to consume oxygen, and it changed the patterns of gene expression.
In all these ways, the “bad” white cells came to resemble “good” brown cells.
The scientists hope that one day the discovery might lead to a new treatment to reduce obesity and prevent diabetes.
“It’s conceivable that one would be able to target this pathway with a drug, to push white fat to become brown fat and thereby treat obesity.”
Dr. Zoltan P. Arany
Dr. Arany points out that until now, this process has not been well understood, but these results shed new light on how it works.
The authors admit that there is still a long way to go in understanding the process, and they plan to carry out more research into the nature of this pathway and other, related signaling pathways.