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

Abstract

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

Platelet-Activating Factor Receptor Ligands Protect Tumor Cells from Radiation-Induced Cell Death

“…The lipid extracts from the irradiated cultures obtained as described in Section “ Materials and Methods ” were then assayed for their capacity to activate PAFR. For this purpose, we developed an assay with carcinoma cells transfected with PAFR (KBP) which secrete (IL-8) in response to receptor activation ( 33 , 34 ). A concentration response curve to the PAFR agonist methylcarbamyl PAF was performed and used to calculate the concentration of PAFR-like lipids present in the supernatants of irradiated cells.…”

Breast milk alkylglycerols sustain beige adipocytes through adipose tissue macrophages

“…Supporting this scenario, the lack of PTAFR protects mice from diet-induced AT inflammation (55). However, the absence of PTAFR also increases lipogenesis (55), and PTAFR-deficient mice develop age-related obesity and are more susceptible to diet-induced obesity than WT mice (54,77,78). Conversely, mice overexpressing human PLA2G2A, a major enzyme of PAF remodeling, are protected from diet-induced obesity and present increased thermogenesis (49).…”

PAFR activation of NF-κB p65 or p105 precursor dictates pro- and anti-inflammatory responses during TLR activation in murine macrophages

“…Impaired IL-10 responses have been linked to human diseases, including inflammatory bowel diseases, arthritis, asthma, and psoriasis293031. PAFR KO mice also exhibit sterile inflammation and insulin resistance by increasing pro-inflammatory macrophages in the adipose tissue32. Thus, the PAF/IL-10 axis might have an important role in preserving homeostasis by down regulating inflammation.…”