Prostaglandin profiling reveals a role for haematopoietic prostaglandin D synthase in adipose tissue macrophage polarisation in mice and humans

Virtue, Sam; Masoodi, Mojgan; Weijer, B.A.M. de; Eijk, Marco van; Mok, Crystal Y.L.; Eiden, Michael; Dale, Martin; Pirraco, Ana; Serlie, Mireille J.; Griffin, Julian L.; Vidal-Puig, António

doi:10.1038/ijo.2015.34

Cited by 38 publications

(34 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We also found that the tissue levels of PGE 2 were significantly reduced in obese mice. This is consistent with previous studies of HFD on adipose tissue levels of PGE 2 (). The biological significance of PGE 2 remains to be determined.…”

Section: Discussionsupporting

confidence: 93%

Lipidomic profiling of high‐fat diet‐induced obesity in mice: Importance of cytochrome P450‐derived fatty acid epoxides

Wang

Yang

et al. 2016

Obesity

View full text Add to dashboard Cite

Objective: Enzymatic metabolism of polyunsaturated fatty acids leads to formation of bioactive lipid metabolites (LMs). Previous studies have shown that obesity leads to deregulation of LMs in adipose tissues. However, most previous studies have focused on a single or limited number of LMs, and few systematical analyses have been carried out. Methods: A LC-MS/MS-based lipidomics approach was used, which can analyze >100 LMs produced by cyclooxygenase, lipoxygenase, and cytochrome P450 (CYP) enzymes, to analyze the profile of LMs in high-fat diet-induced obesity in mice. Results: LC-MS/MS showed that high-fat feeding significantly modulated profiles of LMs in adipose tissues. Among the three major polyunsaturated fatty acid metabolizing pathways (cyclooxygenase, lipoxygenase, and CYP), CYP-derived fatty acid epoxides were the most dramatically altered LMs. Almost all types of fatty acid epoxides were reduced by 70% to 90% in adipose tissues of high-fat diet-fed mice. Consistent with the reduced levels of fatty acid epoxides, the gene expression of several CYP epoxygenases, including Cyp2j5, Cyp2j6, and Cyp2c44, was significantly reduced in adipose tissues of high-fat diet-fed mice. Conclusions: Results show that CYP-derived fatty acid epoxides are the most responsive LMs in highfat diet-induced obesity, suggesting that these LMs could play critical roles in obesity.

show abstract

Section: Discussionsupporting

confidence: 93%

Lipidomic profiling of high‐fat diet‐induced obesity in mice: Importance of cytochrome P450‐derived fatty acid epoxides

Wang

Yang

et al. 2016

Obesity

View full text Add to dashboard Cite

show abstract

“…As a model for assessing whether PGD 2 itself is able to suppress inflammatory cell activation, we treated naïve or polarized bone marrow-derived macrophages (BMMs) in vitro with PGD 2. RNA-seq analysis of naïve BMMs treated with PGD 2 reveals induction of anti-oxidant genes and, as previously reported, a shift towards an anti-inflammatory macrophage phenotype (Figure S13A-B) (40). Lipopolysaccharide (LPS) induces a strong pro-inflammatory response in macrophages ( Figure S13C), and subsequent treatment with PGD 2 resulted in 322 genes being differentially expressed between control and LPS/PGD 2 -treated BMM ( Figure S13D, File S4).…”

Section: Pgd 2 Restrains Disease Progression By Promoting Environmentsupporting

confidence: 84%

Tuft cells restrain pancreatic tumorigenesis through paracrine eicosanoid signaling

DelGiorno

Chung

et al. 2019

Preprint

View full text Add to dashboard Cite

Despite numerous advances in our understanding of pancreatic ductal adenocarcinoma (PDA) genetics and biology, this disease is expected to become the second leading cause of cancer-related U.S. deaths within the next few years. Incomplete understanding of how it arises precludes development of early detection and interception strategies to improve therapeutic outcomes. Acinar to ductal metaplasia involving genesis of tuft cells is one early step in PDA formation, but their functional significance has remained obscure due to their rarity and a lack of methods and relevant animal models for their molecular and functional analysis. Here, we show that deletion of tuft cell master regulator Pou2f3 eliminates pancreatic tuft cells and increases fibrosis, alters immune cell activation, and accelerates disease progression. We demonstrate that tuft cell expression of the prostaglandin D 2 synthase Hpgds restrains pancreatic disease progression in early stages by inhibiting stromal activation. Analyses of human data sets are consistent with mouse studies. We propose that tuft cells and, by inference, the associated metaplastic lesions, play a protective role early in pancreatic tumorigenesis. Significance:We find that tuft cell formation in response to oncogenic Kras is protective and restrains tumorigenesis through local production of anti-inflammatory substances, including paracrine prostaglandin D 2 signaling to the stroma. Our findings establish tuft cells as a metaplasia-induced tumor suppressive cell type. Introduction:Chemical or mechanical injury of the pancreas results in a cell state-switching event termed acinar to ductal metaplasia (ADM) where digestive enzyme producing acinar cells dedifferentiate into proliferative ductal-like cells to restore pancreas homeostasis. This process is perturbed during neoplastic progression, where, in mouse models, initiating Kras mutations prevent tissue healing and, instead, ADM is thought to progress to pancreatic intraepithelial neoplasia (PanIN) and then pancreatic ductal adenocarcinoma (PDA). This is an example of Dvorak's thesis, which states that cancer represents the ever-healing wound (1).The profound difference between the normal healing process and the perturbed response engendered by oncogene activation raises the important question of whether key cell types that result from ADM impact cancer progression. Here, we investigate the role of tuft cells as they appear in response to oncogeneinduced metaplasia in a number of cancers of human significance including lung, stomach, intestine, and pancreas (2-6).Tuft cells are solitary chemosensory cells found throughout the hollow organs of the respiratory and digestive tracts. They are readily identified by their striking morphological features, including long, blunt microvilli, deep actin rootlets, and an extensive tubulovesicular system in the supranuclear cytoplasm (7).Their expression of taste, neuronal, and inflammatory cell signaling factors is thought to enable monitoring of intraluminal homeostasis and to achieve loc...

show abstract

“…HDL has antioxidant and anti-inflammatory properties 40 . Prostaglandin D2 is another eicosanoid produced in macrophages that promotes M2 differentiation and is positively correlated with insulin sensitivity 41 .…”

Section: Macrophage Functions In Lean Tissuementioning

confidence: 99%

Macrophage functions in lean and obese adipose tissue

2017

View full text Add to dashboard Cite

Summary Interactions between macrophages and adipocytes influence both metabolism and inflammation. Obesity-induced changes to macrophages and adipocytes lead to chronic inflammation and insulin resistance. This paper reviews the various functions of macrophages in lean and obese adipose tissue and how obesity alters adipose tissue macrophage phenotypes. Metabolic disease and insulin resistance shift the balance between numerous pro- and anti-inflammatory regulators of macrophages and create a feed-forward loop of increasing inflammatory macrophage activation and worsening adipocyte dysfunction. This ultimately leads to adipose tissue fibrosis and diabetes. The molecular mechanisms underlying these processes have therapeutic implications for obesity, metabolic syndrome, and diabetes.

show abstract

Prostaglandin profiling reveals a role for haematopoietic prostaglandin D synthase in adipose tissue macrophage polarisation in mice and humans

Cited by 38 publications

References 49 publications

Lipidomic profiling of high‐fat diet‐induced obesity in mice: Importance of cytochrome P450‐derived fatty acid epoxides

Lipidomic profiling of high‐fat diet‐induced obesity in mice: Importance of cytochrome P450‐derived fatty acid epoxides

Tuft cells restrain pancreatic tumorigenesis through paracrine eicosanoid signaling

Macrophage functions in lean and obese adipose tissue

Contact Info

Product

Resources

About