A platelet-activating factor (PAF) receptor deficiency exacerbates diet-induced obesity but PAF/PAF receptor signaling does not contribute to the development of obesity-induced chronic inflammation

Yamaguchi, Masahiko; Matsui, Masanao; Higa, Ryoko; Yamazaki, Yoji; Ikari, Akira; Miyake, Masaki; Miwa, Masao; Ishii, Satoshi; Sugatani, Junko; Shimizu, Takao

doi:10.1016/j.bcp.2014.12.022

Cited by 15 publications

(19 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CD36 (scavenger receptor) and PAFR (G-protein coupled receptor) differ in their expression patterns, signaling cascades, and functions (23, 24). Individually, these receptors are immunomodulatory in diseases involving PC-expressing bacteria, helminths, apoptotic cells, and oxidized lipids (23–30). Additionally, some evidence indicates that CD36 and PAFR synergistically promote the removal of apoptotic cells (28).…”

Section: Introductionmentioning

confidence: 99%

CD36 and Platelet-Activating Factor Receptor Promote House Dust Mite Allergy Development

Patel

Kearney

2017

The Journal of Immunology

View full text Add to dashboard Cite

Over 89% of asthmatic children in underdeveloped countries demonstrate sensitivity to house dust mites (HDM). The allergic response to HDM is partially mediated by epithelial cell-derived cytokines that activate group-2 innate lymphoid cells (ILC2s), induce migration and activation of dendritic cells (DCs), and promote effector differentiation of HDM-specific TH2 cells. However, the contribution of innate receptor engagement on epithelial or dendritic cells by HDM that ultimately mediates said innate and adaptive allergic responses is poorly understood. We and others have demonstrated that HDM express phosphorylcholine (PC) moieties. The major PC receptors involved in immune responses include CD36 and platelet activating factor receptor (PAFR). Because both CD36 and PAFR are expressed by epithelial cells and DCs, and expression of these receptors is higher in human asthmatics, we determined whether engagement of CD36 or PAFR on epithelial or dendritic cells contributes to HDM allergy development. Testing bone marrow chimeric mice revealed that CD36 engagement on radioresistant cells and PAFR engagement on both radioresistant and radiosensitive cells in the lung promote allergic responses to HDM. Additionally, passive anti-PC IgM antibodies administered intratracheally with HDM decreased allergen uptake by epithelial and APCs in the lungs of C57BL/6 mice, but not CD36−/− or PAFR−/− mice. These results show that CD36 and PAFR are important mediators of HDM allergy development, and inhibiting HDM engagement with PC receptors in the lung protects against allergic airway disease.

show abstract

Section: Introductionmentioning

confidence: 99%

CD36 and Platelet-Activating Factor Receptor Promote House Dust Mite Allergy Development

Patel

Kearney

2017

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Recently, Yamaguchi et al demonstrated that the knock down of PAFR in mice results in increased adiposity and increased susceptibility to diet-induced obesity (17). Overall, their results suggest that the anti-obesity effect of PAFR is due to impaired energy expenditure.…”

Section: Introductionmentioning

confidence: 70%

“…Using a different mouse strain (C57BL/6) to that employed in our study, Yamagushiet al (17) demonstrated that the deficiency of PAFR exacerbated dietinduced glucose intolerance and no difference was found between WT and PAFKRO fed the SD. In our study, using the Balb/c background, we demonstrated that PAFRKO mice fed in SD were already glucose intolerant and hepatic insulin resistant, as observed by reduced insulin-induced AKT phosphorylation.…”

Section: Discussionmentioning

confidence: 99%

“…Overall, their results suggest that the anti-obesity effect of PAFR is due to impaired energy expenditure. Regarding WAT inflammation, they found that the CD11c+ macrophage (M1) population was increased in PAFR-deficient mice, although they did not find any increased levels of pro-inflammatory markers (17,18). Contrarily, Menezes-Garcia et al found that PAFR deficiency resulted in decreased inflammation in the adipose tissue and improved glucose metabolism (19).…”

Section: Introductionmentioning

confidence: 99%

“…For example, high fat diet increased adiposity in both male and female rats but, whereas the male developed insulin resistance, the female maintained insulin sensitivity (20). Meneses-Garcia et al used male C57Bl/6 and high-refined carbohydrate-containing diet whereas Yamagushi et al, used C57Bl/6 and hight fat diet (60% fat) (17,19). Balb/c also differ from C57Bl/6 mice in the response to PAF, since Balb/c mice are more resistant to shock induced by intravenous injection of PAF (21).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

PAFR in adipose tissue macrophages is associated with anti-inflammatory phenotype and metabolic homoeostasis

et al. 2016

View full text Add to dashboard Cite

PAFR in adipose tissue macrophages is associated with anti-inflammatory phenotype and metabolic homoeostasis. Clinical Science, 130(8), pp. 601-612. (doi:10.1042/cs20150538) This is the author's final accepted version.There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.http://eprints.gla.ac.uk/120744/ cells. Blood monocytes of PAFRKO mice also exhibited a pro-inflammatory phenotype (increased frequency of Lys6C+.cells) and PAFR-ligands were detected in the serum of both PAFRKO and WT. Regarding metabolic parameters, compared to WT, PAFRKO mice had: i) higher weight gain andserum glucose concentration levels; ii) decreased insulin-stimulated glucose disappearance; iii) insulin resistance in the liver; iv) increased expression of Ldlr in the liver. In mice fed HFD, some of these changes were potentiated, particularly in the liver. Thus, it seems that endogenous ligands of PAFR are responsible for maintaining the anti-inflammatory profile of blood monocytes and adipose tissue macrophages under physiological conditions. In the absence of PAFR signaling, monocytes and macrophages acquire pro-inflammatory phenotype, resulting in adipose tissue inflammation and metabolic dysfunction. SummaryWe found an essential role of PAFR in adipose tissue macrophages. The PAFRdeficiency leads to infiltration of pro-inflammatory macrophages in the adipose tissue resulting in weight gain, reduced glucose tolerance, hepatic insulin resistance, followed by hepatic steatosis.Short Title: PAFR is associated with anti-inflammatory macrophages and glucose metabolism

show abstract

Mice lacking myotubularin-related protein 14 show accelerated high-fat diet-induced lipid accumulation and inflammation

Liu

Peng

et al. 2016

J Physiol Biochem

View full text Add to dashboard Cite

The phosphoinositide phosphatase, myotubularin-related protein 14 (MTMR14), has been reported to play an important role in the regulation of muscle performance, autophagy, and aging in mice. We previously showed that MTMR14-knockout (KO) mice gain weight earlier than their wild-type (WT) littermates even on a normal chow diet (NCD), suggesting that this gene might also be involved in regulating metabolism. In the present study, we evaluated the effect of MTMR14 deficiency on high-fat diet (HFD)-induced obesity, lipid accumulation, metabolic disorders, and inflammation in WT and MTMR14-KO mice fed with NCD or HFD. To this end, MTMR14-KO mice fed with HFD showed significantly increased body weight, blood glucose levels, serum triglyceride (TG) levels, and total cholesterol (TC) levels as compared to their age-matched WT control. Additionally, lipid accumulation also increased in the KO mice. Simultaneously, the expression of metabolism-associated genes (Glut4, adiponectin, and leptin) was different in the liver, muscle, and fatty tissue of MTMR14-KO mice fed with HFD. More importantly, the expression of several inflammation-associated genes (TNF-α, IL-6, IL-1β, and MCP-1) dramatically increased in the liver, muscle, and fatty tissue of MTMR14-KO mice relative to control. Taken together, these results suggest that MTMR14 deficiency accelerates HFD-induced metabolic dysfunction and inflammation. Furthermore, the results showed that exacerbated metabolic dysfunction and inflammation may be regulated via the PI3K/Akt and ERK signaling pathways.

show abstract

A platelet-activating factor (PAF) receptor deficiency exacerbates diet-induced obesity but PAF/PAF receptor signaling does not contribute to the development of obesity-induced chronic inflammation

Cited by 15 publications

References 39 publications

CD36 and Platelet-Activating Factor Receptor Promote House Dust Mite Allergy Development

CD36 and Platelet-Activating Factor Receptor Promote House Dust Mite Allergy Development

PAFR in adipose tissue macrophages is associated with anti-inflammatory phenotype and metabolic homoeostasis

Mice lacking myotubularin-related protein 14 show accelerated high-fat diet-induced lipid accumulation and inflammation

Contact Info

Product

Resources

About