RT Journal Article
SR Electronic
T1 Dietary fatty acids promote lipid droplet diversity through seipin enrichment in an ER subdomain
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 424663
DO 10.1101/424663
A1 Zhe Cao
A1 Yan Hao
A1 Yiu Yiu Lee
A1 Pengfei Wang
A1 Xuesong Li
A1 Kang Xie
A1 Wen Jiun Lam
A1 Yifei Qiu
A1 Guanghou Shui
A1 Pingsheng Liu
A1 Jianan Qu
A1 Byung-Ho Kang
A1 Ho Yi Mak
YR 2018
UL http://biorxiv.org/content/early/2018/09/22/424663.abstract
AB Exogenous metabolites from microbial and dietary origins have profound effects on host metabolism. Here, we report that a sub-population of lipid droplets (LDs), which are conserved organelles for fat storage, is defined by metabolites-driven targeting of the C. elegans seipin ortholog, SEIP-1. Loss of SEIP-1 function reduced the size of a subset of LDs while over-expression of SEIP-1 had the opposite effect. Ultrastructural analysis revealed SEIP-1 enrichment in an endoplasmic reticulum (ER) subdomain, which co-purified with LDs. Analyses of C. elegans and bacterial genetic mutants indicated a requirement of polyunsaturated fatty acids (PUFAs) and microbial cyclopropane fatty acids (CFAs) for SEIP-1 enrichment, as confirmed by dietary supplementation experiments. In mammalian cells, heterologous expression of SEIP-1 promoted lipid droplet expansion from ER subdomains in a conserved manner. Our results suggest that microbial and polyunsaturated fatty acids serve unexpected roles in regulating cellular fat storage by enforcing LD diversity.