Scientists have discovered the genetic mechanism through which calorie-storing white fat cells can be reprogrammed to become more like calorie-burning brown fat cells. The finding could lead to new drugs that target the mechanism to help treat obesity.
Like other mammals, humans have lots of white fat and not so much brown fat. White fat stores excess calories for release to energy-hungry organs during fasting, whereas brown fat is mostly used to burn calories to produce heat.
When we regularly consume more calories than we use, the excess calories build up in white fat, and we become overweight and obese. Too much white fat around the abdomen is linked to metabolic dysfunction, insulin resistance and heart disease.
In recent years, scientists have become increasingly interested in the possibility of changing the balance between white fat and brown fat as a way to tackle obesity. One such avenue is the genetic reprogramming of white fat cells into brown fat cells.
Now, in a new study led by the University of Southern Denmark and published in the journal Genes & Development, researchers describe their success in reprogramming energy-storing white fat cells to behave more like brown fat cells. They call the reprogrammed cells “brite” fat cells — where “brite” is short for “brown in white.”
Genetic reprogramming creates ‘brite’ or ‘brown in white’ fat cells
The goal the researchers are pursuing is to transform white fat cells in white fat tissue into brite fat cells that burn calories as heat instead of storing it.
Susanne Mandrup, a professor in the Department of Biochemistry and Molecular Biology at the University of Southern Denmark, explains their work with fat cells or adipocytes:
“We have investigated how the genome of white adipocytes is reprogrammed during browning using advanced genome sequencing technologies. We stimulated browning in human white adipocytes by a drug used to treat type II diabetes and compared white and ‘brite’ fat cells.”
She says they found that “brite” fat cells “have distinct gene programs which, when active, make these cells particularly energy-consuming.”
By finding the areas of the genome that are directly involved in the reprogramming, the team has also identified another important factor — a gene found in all fat cells that is required for the reprogramming to take place. The essential gene is called regulatory protein KLF11 (Kruppel Like Factor- 11).
Researchers foresee ‘browning factors’ as future targets for obesity drugs
First author and PhD student Anne Loft says finding the mechanism behind brite fat cells and the areas of the genome involved potentially means, “in the future we can target drugs to activate the genomic regions and browning factors like KLF11 in the treatment of obesity.”
In a related study published in August, researchers succeeded for the first time in very specifically distinguishing the various types of fat cells — white, brown, and beige — on the basis of their surface proteins. This is raising hope for a new method to treat those suffering from obesity and diabetes.
According to the team behind that study, “[b]ecause of its function as the body’s thermal power station, brown adipose tissue has the ability to burn large quantities of energy that otherwise would be stored in white adipose tissue as fat.” For this reason, activation of brown adipose tissue using drugs offers an attractive approach to treat obesity and the illnesses that result from it, such as type 2 diabetes.