A study from the University of Fribourg sheds some light on how our cells store fat. These results are an important step towards a better understanding of the mechanisms underlying obesity, one of today's major public health issues.
Fat plays an essential role in our body. Our cells use fat to store energy in the form of fatty acids, a source of energy that can then be used when needed. The body stores fat in two ways: either in tissues entirely dedicated to this role, the adipose tissue, or inside other types of cells in small vacuoles filled with fatty acids called ««lipid droplets».
While these reserves are essential for our survival, excess fat storage in cells can lead to obesity which is linked to various health issues including cardiovascular diseases and diabetes. However, many details of the cellular and molecular mechanisms that control fat storage remain a mystery.
Professor Stefano Vanni and his team from the Department of Biology at the University of Fribourg have been investigating how lipid droplets form in cells. In particular, their efforts focused on a protein called seipin, which is involved in the process and which underlies a very serious type of disease related to fat metabolism, congenital lipodystrophy. In two recent publications, the team has demonstrated how seipin initiates the formation of lipid droplets and how the fatty acids that make up cell membranes play a role in this process.
Cells, yeast and computers
For the first time, the researchers have described this process with molecular detail. To do this, they used a combination of three approaches: experiments on human cells, experiments on yeast genetically modified for studying the behaviour of the seipin protein, and detailed computer simulations. The latter approach is the specialty of Professor Stefano Vanni: vast molecule-by-molecule simulations of the complex processes of life at the cellular level. These simulations allow a detailed and mechanistic understanding of molecular processes beyond what is accessible through laboratory experiments.
Millions for research on fat metabolism
For his pioneering work in this field, Professor Vanni has received two important grants: an Eccellenza grant from the Swiss National Science Foundation and a grant from the European Research Council – a total of more than four million francs for the work of his research group.
«Having a better understanding of the formation of lipid droplets in cells and the role of seipin is an important step in the management of weight problems and obesity», explains Professor Vanni. «Of course, we can't simply interfere with the work of this protein, because the formation of lipid droplets for energy storage is essential to the body. Without it, fatty acids accumulate in the cell and eventually kill it. But a finer understanding at the molecular level opens up possibilities for promoting or slowing down certain mechanisms and provides new tools in the management of obesity-related problems.»
The results were published in the journals eLife and PNAS on 1 February and 5 March 2021 respectively.
Valeria Zoni, Rasha Khaddaj, Ivan Lukmantara, Wataru Shinoda, Hongyuan Yang, Roger Schneiter, Stefano Vanni. Seipin accumulates and traps diacylglycerols and triglycerides in its ring-like structure. 2021. Proceedings of the National Academy of Sciences March 2021, 118 (10) DOI: 10.1073/pnas.2017205118
Valeria Zoni, Rasha Khaddaj, Pablo Campomanes, Abdou Rachid Thiam, Roger Schneiter, Stefano Vanni. Pre-existing bilayer stresses modulate triglyceride accumulation in the ER versus lipid. 2021. eLife 2021;10:e62886 DOI: 10.7554/eLife.62886