Scientists reprogram fat cells to burn off calories

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.

Researchers reprogrammed calorie-storing white fat cells into energy-burning brown fat cells.
Image credit: University of Southern Denmark.

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.

Scientists are 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.

The research team 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."

They say 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

The researchers also say 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."

If you think of genes as being the "hardware" of genetic programming, then epigenes are like the "software" - they change the behavior of the hardware, for instance depending on environment changes, using chemical switches in a process known as methylation.

The researchers compared the muscle of trained and untrained legs in cyclists that had cycled with one leg only for 3 months and found strong associations between the change in activity of 4,000 genes and epigenetic methylation.

References:

Browning of human adipocytes requires KLF11 and reprogramming of PPARγ superenhancers, Anne Loft et al., Genes & Dev, doi:10.1101/gad.250829.114, published online 12 December 2014, abstract.
University of Southern Denmark press release accessed 15 December 2014 via EurekAlert.