Prostaglandin profiling reveals a role for haematopoietic prostaglandin D synthase in adipose tissue macrophage polarisation in mice and humans
Author(s)
Type
Journal Article
Abstract
BACKGROUND/OBJECTIVES: Obesity has been associated with both changes in adipose tissue lipid metabolism and inflammation. A key class of lipid-derived signalling molecules involved in inflammation are the prostaglandins. In this study, we aimed to determine how obesity affects the levels of prostaglandins within white adipose tissue (WAT) and determine which cells within adipose tissue produce them. To avoid the effects of cellular stress on prostaglandin levels, we developed a multivariate statistical approach in which metabolite concentrations and transcriptomic data were integrated, allowing the assignment of metabolites to cell types. SUBJECTS/METHODS: Eicosanoids were measured by liquid chromatography-tandem mass spectrometry and mRNA levels using real-time PCR. Eicosanoid levels and transcriptomic data were combined using principal component analysis and hierarchical clustering in order to associate metabolites with cell types. Samples were obtained from C57Bl/6 mice aged 16 weeks. We studied the ob/ob genetically obese mouse model and diet-induced obesity model. We extended our results in mice to a cohort of morbidly obese humans undergoing bariatric surgery. RESULTS: Using our modelling approach, we determined that prostglandin D₂ (PGD₂) in adipose tissue was predominantly produced in macrophages by the haematopoietic isoform of prostaglandin D synthase (H-Pgds). Analysis of sub-fractionated WAT confirmed that H-Pgds was expressed in adipose tissue macrophages (ATMs). Furthermore, H-Pgds expression in ATMs isolated from lean and obese mice was consistent with it affecting macrophage polarisation. Functionally, we demonstrated that H-PGDS-produced PGD₂ polarised macrophages toward an M2, anti-inflammatory state. In line with a potential anti-inflammatory role, we found that H-PGDS expression in ATMs was positively correlated with both peripheral insulin and adipose tissue insulin sensitivity in humans. CONCLUSIONS: In this study, we have developed a method to determine the cellular source of metabolites within an organ and used it to identify a new role for PGD₂ in the control of ATM polarisation.
Date Issued
2015-07-01
Date Acceptance
2014-12-25
Citation
International Journal of Obesity, 2015, 39 (7), pp.1151-1160
ISSN
0307-0565
Publisher
Springer Nature [academic journals on nature.com]
Start Page
1151
End Page
1160
Journal / Book Title
International Journal of Obesity
Volume
39
Issue
7
Copyright Statement
© 2015 Macmillan Publishers Limited. This work is licensed under a Creative Commons Attribution 4.0International License. The images or other third party material in thisarticle are included in the article’s Creative Commons license, unless indicatedotherwise in the credit line; if the material is not included under the Creative Commonslicense, users will need to obtain permission from the license holder to reproduce thematerial. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/25801691
PII: ijo201534
Subjects
Adipogenesis
Adipose Tissue
Animals
Chromatography, Liquid
Diet
Disease Models, Animal
Eicosanoids
Humans
Inflammation
Lipid Metabolism
Macrophages
Mice
Mice, Inbred C57BL
Mice, Obese
Obesity
Prostaglandin D2
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2015-03-25