1.9 billion people in the world are overweight. Of these, 650 million people have obesity. This increases the risk of complications such as high blood pressure or cancer. The team led by Professor Martin Klingenspor at the Technical University of Munich (TUM) is researching the impact of fat metabolism on our health. Together with Professor Bart Deplancke's research group at the École Polytechnique Fédérale de Lausanne (EPFL), a network of genes has now been identified that could convert energy-storing fat into energy-burning fat.
Our fat cells, so-called adipocytes, play a central role in the regulation of the energy balance. "Adipocytes are not only energy stores for scarce times, they also release hormones into the blood that regulate the metabolism and the feeling of hunger and satiety through the brain and other organs," said Klingenspor, Chair of Molecular Nutritional Medicine at Else Kröner-Fresenius- Center of the TUM.
White, beige or brown - the colors of the fat cells affect health
There are different types of adipose tissue in the body that differ in color. White fat cells primarily serve as energy stores. Brown and beige fat cells can convert food energy into heat. This process is known as tremor-free thermogenesis and is used by small mammals and human newborns to maintain body temperature.
The appearance and activity of brown and beige fat cells differs between individuals. For people with many of these thermogenic fat cells, there is evidence of a lower risk of obesity and metabolic diseases. In particular, the formation of beige fat cells in white adipose tissue could have a positive effect on health.
The ability of white fat to brown is genetically determined
"We want to understand how thermogenic fat cells develop, that is, how beige fat cells develop in white fat tissue," says Klingenspor. With the "tanning" of the white adipose tissue, an energy-storing organ could be partially converted into an energy-releasing organ and thus promote metabolic health.
The development of beige fat cells is controlled by a genetic program that has so far hardly been understood. Klingenspor's group found out which genes could explain the differences in cell differentiation, i.e. the development of beige fat cells, in a systematic patterning of fat cells of genetically different mouse strains. Strains were selected that differ in their ability to tan the white adipose tissue.
New possibilities thanks to transcriptome and network analysis
By sequencing all transcripts in a cell with the next generation sequencing technology, the genome-wide activity of all genes can be recorded in one go.
In the current study, the team from TUM and EPFL compared the transcriptomes of the fat cells from the different mouse strains. The study goes beyond other work in this field because it not only identifies individual important factors, but also links them together in a systematic network.
This enabled the team for the first time to provide a systematic overview of the network of cell-intrinsic, regulatory mechanisms that underlie the development of beige fat cells.
"Now we have unique insights into the genetic architecture of the development of beige fat cells," said Klingenspor. "In a next step, what we were able to demonstrate in a cell culture will be checked 'in vivo', ie in living organisms," Klingenspor gives an outlook.
Materials provided by Technical University Munich.