Scientists explore lipid metabolism with simulations and experiments

snapshot from simulation

Proper regulation of lipid metabolism and storage is critical for our health. A central role in these processes is played by so-called lipid droplets, which are a sort of storage system for lipids and also serve as cellular energy suppliers. To better understand these droplets and how they may affect the development of diseases, Biophysicist Stefano Vanni performed molecular dynamics simulations using PRACE supercomputing resources. The results shed new light on the vital work of phospholipids, and on a mysterious protein.

In humans and animals, fat cells fulfil vital tasks protecting our organs and serving as a source of reserve energy. They produce and store fat in specific organelles, meaning specialised cellular subunits, called lipid droplets, which are involved in lipid metabolism of every single cell of the human organism. “The role of lipid droplets is critical. When lipid storage is poorly regulated, pathologies such as obesity, lipodystrophy and cancer develop,” says Stefano Vanni, a biophysicist at the University of Fribourg.

Simulating lipid metabolism

To better understand the mechanisms involved in lipid storage, Vanni and his team performed coarse-grain molecular dynamics simulations using a PRACE allocation on the supercomputer “Piz Daint” at the Swiss National Supercomputing Centre CSCS. In a first study, the researchers investigated lipid droplet formation. By combining simulations and in vivo fluorescence microscopy experiments, they showed that the so-called phospholipids, which are the principal component of membranes of cells and organelles, are directly involved in the regulating processes that determine if lipid droplets are formed or not.

The team went on to investigate the role of a membrane protein called seipin, which was discovered only two decades ago in connection with a rare disease called lipodystrophy, in which the affected individuals are unable to store lipids. One of seipin’s mysteries, according to Vanni, is that when the protein is disabled, either very large or very small lipid droplets are formed, making it difficult to understand the protein’s function. Among else, the team’s simulations now showed that seipin traps and accumulates certain lipids called triglycerides within its ring-shaped structure and that, if mutations are introduced in the in this specific trapping region, formation of lipid droplets is hindered.

Go on to read the full story on the CSCS website.

More information about the research of Stefano Vanni’s group:

Project Title:
16th call: LDbud – Lipid Droplet Biogenesis
21st call: FATstor – The role of Bernardinelli-Seip congenital lipodystrophy type 2 protein (BSCL2 – seipin) and its pathological variants in intracellular fat accumulation

Resources awarded:
16th call: 68 million core hous on Piz Daint hosted by CSCS, Switzerland
21st call: 68 million core hous on Piz Daint hosted by CSCS, Switzerland

Research field: Biochemistry, Bioinformatics & Life Sciences

References:
Zoni V, Khaddaj R, Campomanes P, Thiam AR, Schneiter R & Vanni S: Pre-existing bilayer stresses modulate triglyceride accumulation in the ER versus lipid droplets, eLife (2021) DOI: 10.7554/eLife.62886

Zoni V, Khaddaj R, Lukmantara I, Shinoda W, Yang H, Schneiter R & Vanni S: Seipin accumulates and traps diacylglycerols and triglycerides in its ring-like structure, PNAS (2021) DOI: 10.1073/pnas.2017205118

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