Cell Transformation and the Fight Against Fat
By Kevin Ritchart
Researchers from McGill University in Montreal have discovered a means of stimulating the body to burn fat rather than store it, which could aid in the evergrowing battle against obesity, diabetes and cardiovascular diseases.
Earlier this year, McGill researchers published a study that centered on a protein called folliculin and its role in controlling the activity of fat cells. By eliminating the gene that produces folliculin in the fat cells of mice, researchers were able to switch the cell’s primary function from storing fat to burning it.
The process is known as the “browning” of fat cells. The color of brown fat is derived from iron-rich mitochondria, and the browner a cell is, the more active it is in the body from a metabolic perspective. The primary role of brown fat is to burn energy that produces heat, which helps us maintain a constant body temperature. Conversely, white fat’s chief function is energy storage.
Scientists recently found a new type of fat tissue with characteristics that fall somewhere between healthy brown fat and the more harmful white variety. This so-called beige fat is able to act like brown fat in the presence of certain stimuli, such as exposure to extreme cold. As these beige fat cells become more active within the body, it’s less likely that we’ll accumulate the types of unhealthy at deposits that lead to obesity. Now the challenge becomes how to consistently convert white fat cells into the energyburning beige ones.
“Conversion from white fat cells to beige or brown fat cells is a very desirable effect in the obesity, diabetes, and metabolic syndrome indications, since excess energy in the body is not stored in fat tissue but is burned in brown or beige fat tissue,” said professor Arnim Pause, the senior author of the McGill study.
Pause and his research team bred mice to have fat cells that would not produce folliculin. They fed both normal and folliculin-deficient mice a high-fat diet for a period of 14 weeks. The normal mice gained weight at a rapid pace, but the mice without folliculin stayed thin and did not exhibit the same elevated insulin and triglyceride levels.
By measuring the rates of both oxygen consumption and carbon dioxide production, researchers were able to determine that the folliculin-deficient mice were burning more fat. By the end of the trial, the folliculin-deficient mice had smaller white fat cells and less white fat tissue. Furthermore, the additional energy being produced resulted in the mice better able to withstand cold temperatures.
This discovery builds on existing knowledge that a pair of proteins — PGC- 1a and ERRa — are involved in regulating the mitochondria of fat cells. The removal of folliculin gives an enzyme called AMPK the ability to activate the proteins, thereby adding to the number and the work rate of the mitochondria within the fat cell. The result of this type of manipulation is a metabolic reprogramming of fat tissue, turning it from fat storage into fat burner. Because researchers were able to determine the folliculin pathway, new medications can be developed to stimulate the browning process.
“Since that mechanism involves a class of proteins that can be targeted by drugs that are readily absorbed in the body, one implication is that a drug could be developed to stimulate the activity of beige/ brown fat cells and thus help manage obesity and other metabolic disorders,” researcher Vincent Giguère said.