Dietary S. maltophilia induces supersized lipid droplets by enhancing lipogenesis and ER-LD contacts in C. elegans

Kang Xie; Yangli Liu; Xixia Li; Hong Zhang; Shuyan Zhang; Ho Yi Mak; Pingsheng Liu

doi:10.1080/19490976.2021.2013762

Dietary S. maltophilia induces supersized lipid droplets by enhancing lipogenesis and ER-LD contacts in C. elegans

Gut Microbes. 2022 Jan-Dec;14(1):2013762. doi: 10.1080/19490976.2021.2013762.

Authors

Kang Xie^{1

2}, Yangli Liu^{1

2}, Xixia Li¹, Hong Zhang^{1

2}, Shuyan Zhang¹, Ho Yi Mak³, Pingsheng Liu^{1

2}

Affiliations

¹ National Laboratory of Biomacromolecules, Cas Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
² University of Chinese Academy of Sciences, Beijing, China.
³ Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China.

Abstract

Dietary and symbiotic bacteria can exert powerful influence on metazoan lipid metabolism. Recent studies have emerged that microbiota have a role in animal obesity and related health disorders, but the mechanisms by which bacteria influence lipid storage in their host are unknown. To reduce the complexity of the relationship between gut microbiota and the host, Caenorhabditis elegans (C. elegans) has been chosen as a model organism to study interspecies interaction. Here, we demonstrate that feeding C. elegans with an opportunistic pathogenic bacterium Stenotrophomonas maltophilia (S. maltophilia) retards growth and promotes excessive neutral lipid storage. Gene expression analysis reveals that dietary S. maltophilia induces a lipogenic transcriptional response that includes the SREBP ortholog SBP-1, and fatty acid desaturases FAT-6 and FAT-7. Live imaging and ultrastructural analysis suggest that excess neutral lipid is stored in greatly expanded lipid droplets (LDs), as a result of enhanced endoplasmic reticulum (ER)-LD interaction. We also report that loss of function mutations in dpy-9 in C. elegans confers resistance to S. maltophilia. Dietary S. maltophilia induces supersized LDs by enhancing lipogenesis and ER-LD contacts in C. elegans. This work delineates a new model for understanding microbial regulation of metazoan physiology.

Keywords: Stenotrophomonas maltophilia/obesity/dhs-3/mdt-28/lipid droplet.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Caenorhabditis elegans / genetics
Caenorhabditis elegans / growth & development
Caenorhabditis elegans / metabolism*
Caenorhabditis elegans / microbiology*
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / metabolism
Endoplasmic Reticulum / genetics
Endoplasmic Reticulum / metabolism
Female
Gastrointestinal Microbiome
Lipid Droplets / metabolism*
Lipogenesis*
Male
Stearoyl-CoA Desaturase / genetics
Stearoyl-CoA Desaturase / metabolism
Stenotrophomonas maltophilia / metabolism*
Transcription Factors / genetics
Transcription Factors / metabolism

Substances

Caenorhabditis elegans Proteins
SBP-1 protein, C elegans
Transcription Factors
Stearoyl-CoA Desaturase
fat-6 protein, C elegans
fat-7 protein, C elegans

Grants and funding

This work was supported by the National Natural Science Foundation of China (Grant No. 91857201), the National Key R&D Program of China (Grant No. 2018YFA0800700), other National Key R&D Program of China (Grant No. 2018YFA0800900 and 2016YFA0500100), and other National Natural Science Foundation of China (Grant No. 91954108, 31671402 and U1702288). This work was also supported by the “Personalized Medicines——Molecular Signature-based Drug Discovery and Development”, Strategic Priority Research Program of the Chinese Academy of Sciences, Grant No. “ XDA12040218; This work was also supported by the CAS-Croucher Joint Laboratory Project, Project No. CAS16SC01.