Format

Send to

Choose Destination
FASEB J. 2019 Apr;33(4):4741-4754. doi: 10.1096/fj.201801897R. Epub 2019 Jan 4.

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

Author information

1
Nutriomics Team, INSERM, Unité 1166-Sorbonne Université, Paris, France.
2
ICANalytics Team, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.
3
Integromics Team, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.
4
Micalis Institute, Institut National de la Recherche Aagronomique (INRA)-AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France.
5
Integrative Biology of Atherosclerosis Team, INSERM, Unité 1166-Sorbonne Université, Paris, France.
6
Nutrition Department, Centre de Recherche en Nutrition Humaine (CRNH)-Ile de France, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
7
Newcastle Fibrosis Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.

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.-Kayser, B. D., Lhomme, M., Prifti, E., Da Cunha, C., Marquet, F., Chain, F., Naas, I., Pelloux, V., Dao, M.-C., Kontush, A., Rizkalla, S. W., Aron-Wisnewsky, J., Bermúdez-Humarán, L. G., Oakley, F., Langella, P., Clément, K., Dugail, I. Phosphatidylglycerols are induced by gut dysbiosis and inflammation, and favorably modulate adipose tissue remodeling in obesity.

KEYWORDS:

adipocyte lipolysis; lipidomic profiling; phosphatidylglycerol synthesis; serum phospholipidome

PMID:
30608881
DOI:
10.1096/fj.201801897R

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center