Seipin accumulates and traps diacylglycerols and triglycerides in its ring-like structure

Significance Metabolic disorders related to aberrant fat accumulation, including lipodystrophy and obesity, are a serious health concern. Inside cells, fat accumulates in organelles named lipid droplets (LDs). LDs form in the endoplasmic reticulum (ER), where triglycerides (TG), the most abundant form of fat, are produced. The Berardinelli–Seip congenital lipodystrophy type 2 protein, seipin, has been identified as a key regulator of LD formation, but its mechanism of action remains debated and its molecular details mostly obscure. Here, we use molecular dynamics simulations to investigate the mechanism of seipin action. We find that seipin clusters and traps both TG and its precursor, diacylglycerol. Our results suggest that seipin organizes the lipid composition of specific ER sites to prime them for LD biogenesis.