Loss of the seipin gene perturbs eggshell formation in <i>C. elegans</i>.

SEIPIN, an evolutionary conserved protein, plays pivotal roles during lipid droplet (LD) biogenesis and is associated with various human diseases with unclear mechanisms. Here, we analyzed <i>C. elegans</i> mutants deleted of the sole SEIPIN gene, <i>seip-1</i> Homozygous <i>seip-1</i> mutants displayed penetrant embryonic lethality, which is caused by the disruption of the lipid-rich permeability barrier, the innermost layer of the <i>C. elegans</i> embryonic eggshell. In <i>C. elegans</i> oocytes and embryos, SEIP-1 is associated with LDs and crucial for controlling LD size and lipid homeostasis. The <i>seip-1</i> deletion mutants reduced the ratio of polyunsaturated fatty acids (PUFAs) in their embryonic fatty acid pool. Interestingly, dietary supplementation of selected n-6 PUFAs rescued the embryonic lethality and defective permeability barrier. Accordingly, we propose that SEIP-1 may maternally regulate LD biogenesis and lipid homeostasis to orchestrate the formation of the permeability barrier for eggshell synthesis during embryogenesis. A lipodystrophy allele of <i>seip-1</i> resulted in embryonic lethality as well and could be rescued by PUFA supplementation; these experiments support a great potential of using <i>C. elegans</i> to model SEIPIN-associated human diseases.