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

Zhe Cao, Yan Hao, Chun Wing Fung, Yiu Yiu Lee, Pengfei Wang, Xuesong Li, Kang Xie, Wen Jiun Lam, Yifei Qiu, Ben Zhong Tang, Guanghou Shui, Pingsheng Liu, Jianan Qu, Byung-Ho Kang and Ho Yi Mak ()
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Zhe Cao: The Hong Kong University of Science and Technology
Yan Hao: The Hong Kong University of Science and Technology
Chun Wing Fung: The Hong Kong University of Science and Technology
Yiu Yiu Lee: The Hong Kong University of Science and Technology
Pengfei Wang: The Chinese University of Hong Kong
Xuesong Li: The Hong Kong University of Science and Technology
Kang Xie: Chinese Academy of Sciences
Wen Jiun Lam: The Hong Kong University of Science and Technology
Yifei Qiu: The Hong Kong University of Science and Technology
Ben Zhong Tang: The Hong Kong University of Science and Technology
Guanghou Shui: Chinese Academy of Sciences
Pingsheng Liu: Chinese Academy of Sciences
Jianan Qu: The Hong Kong University of Science and Technology
Byung-Ho Kang: The Chinese University of Hong Kong
Ho Yi Mak: The Hong Kong University of Science and Technology

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: 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 metabolite-modulated targeting of the C. elegans seipin ortholog, SEIP-1. Loss of SEIP-1 function reduces the size of a subset of LDs while over-expression of SEIP-1 has the opposite effect. Ultrastructural analysis reveals SEIP-1 enrichment in an endoplasmic reticulum (ER) subdomain, which co-purifies with LDs. Analyses of C. elegans and bacterial genetic mutants indicate 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, heterologously expressed SEIP-1 engages nascent lipid droplets and promotes their subsequent expansion in a conserved manner. Our results suggest that microbial and polyunsaturated fatty acids serve unexpected roles in regulating cellular fat storage by promoting LD diversity.

Date: 2019
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DOI: 10.1038/s41467-019-10835-4

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