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bioRxiv · 10.1101/424663

Dietary fatty acids promote lipid droplet diversity through seipin enrichment in an ER subdomain

Cao, Z.·Hao, Y.·Lee, Y. Y.·Wang, P.·Li, X.·Xie, K.·Lam, W. J.·Qiu, Y.·Shui, G.·Liu, P.·Qu, J.·Kang, B.-H.·Mak, H. Y.
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Abstract

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.

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Cao, Z., Hao, Y., Lee, Y. Y., Wang, P., Li, X., Xie, K., Lam, W. J., Qiu, Y., Shui, G., Liu, P., Qu, J., Kang, B.-H., Mak, H. Y.. 2018-09-22. Dietary fatty acids promote lipid droplet diversity through seipin enrichment in an ER subdomain. https://doi.org/10.1101/424663

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