Phosphatidylglycerols are induced by gut dysbiosis and inflammation, and favorably modulate adipose tissue remodeling in obesity

Brandon D. Kayser, Marie Lhomme, Edi Prifti, Carla Da Cunha, Florian Marquet, Florian Chain, Isabelle Naas, Véronique Pelloux, Maria Carlota Dao, Anatol Kontush, Salwa W. Rizkalla, Judith Aron-Wisnewsky, Luis G. Bermúdez-Humarán, Fiona Oakley, Philippe Langella, Karine Clément, Isabelle Dugail

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Lipidomic techniques can improve our understanding of complex lipid interactions that regulate metabolic diseases. Here, a serum phospholipidomics analysis identified associations between phosphatidylglycerols (PGs) and gut microbiota dysbiosis. Compared with the other phospholipids, serum PGs were the most elevated in patients with low microbiota gene richness, which were normalized after a dietary intervention that restored gut microbial diversity. Serum PG levels were positively correlated with metagenomic functional capacities for bacterial LPS synthesis and host markers of low-grade inflammation; transcriptome databases identified PG synthase, the first committed enzyme in PG synthesis, as a potential mediator. Experiments in mice and cultured human-derived macrophages demonstrated that LPS induces PG release. Acute PG treatment in mice altered adipose tissue gene expression toward remodeling and inhibited ex vivo lipolysis in adipose tissue, suggesting that PGs favor lipid storage. Indeed, several PG species were associated with the severity of obesity in mice and humans. Finally, despite enrichment in PGs in bacterial membranes, experiments employing gnotobiotic mice colonized with recombinant PG overproducing Lactococcus lactis showed limited direct contribution of microbial PGs to the host. In summary, PGs are inflammation-responsive lipids indirectly regulated by the gut microbiota via endotoxins and regulate adipose tissue homeostasis in obesity.

Original languageEnglish
Pages (from-to)4741-4754
Number of pages14
JournalFASEB Journal
Volume33
Issue number4
DOIs
StatePublished - 2019

Keywords

  • Adipocyte lipolysis
  • Lipidomic profiling
  • Phosphatidylglycerol synthesis
  • Serum phospholipidome

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