| RRC ID |
36755
|
| 著者 |
Yamaguchi M, Matsui M, Higa R, Yamazaki Y, Ikari A, Miyake M, Miwa M, Ishii S, Sugatani J, Shimizu T.
|
| タイトル |
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.
|
| ジャーナル |
Biochem Pharmacol
|
| Abstract |
Platelet-activating factor (PAF) is a well-known phospholipid that mediates acute inflammatory responses. In the present study, we investigated whether PAF/PAF receptor signaling contributed to chronic inflammation in the white adipose tissue (WAT) of PAF receptor-knockout (PAFR-KO) mice. Body and epididymal WAT weights were higher in PAFR-KO mice fed a high-fat diet (HFD) than in wild-type (WT) mice. TNF-α mRNA expression levels in epididymal WAT and the infiltration of CD11c-positive macrophages into epididymal WAT, which led to chronic inflammation, were also elevated in HFD-fed PAFR-KO mice. HFD-fed PAFR-KO mice had higher levels of fasting serum glucose than HFD-fed WT mice as well as impaired glucose tolerance. Although PAF receptor signaling up-regulated the expression of TNF-α and lipopolysaccharide induced the expression of acyl-CoA:lysophosphatidylcholine acyltransferase 2 (LPCAT2) mRNA in bone marrow-derived macrophages, no significant differences were observed in the expression of LPCAT2 mRNA and PAF levels in epididymal WAT between HFD-fed mice and normal diet-fed mice. In addition to our previous finding in which energy expenditure in PAF receptor (PAFR)-deficient mice was low due to impaired brown adipose tissue function, the present study demonstrated that PAF/PAF receptor signaling up-regulated the expression of Ucp1 mRNA, which is essential for cellular thermogenesis, in 3T3-L1 adipocytes. We concluded that the marked accumulation of abdominal fat due to HFD feeding led to more severe chronic inflammation in WAT, which is associated with glucose metabolism disorders, in PAFR-KO mice than in WT mice, and PAF/PAF receptor signaling may regulate energy expenditure and adiposity.
|
| 巻・号 |
93(4)
|
| ページ |
482-95
|
| 公開日 |
2015-2-15
|
| DOI |
10.1016/j.bcp.2014.12.022
|
| PII |
S0006-2952(15)00023-4
|
| PMID |
25577975
|
| MeSH |
Animals
Cells, Cultured
Diet, High-Fat / adverse effects*
Inflammation / metabolism
Inflammation / pathology
Male
Mice
Mice, Knockout
Obesity / metabolism*
Obesity / pathology
Platelet Activating Factor / metabolism*
Platelet Membrane Glycoproteins / deficiency*
Receptors, G-Protein-Coupled / deficiency*
Signal Transduction / physiology*
|
| IF |
4.96
|
| 引用数 |
8
|
|
WOS 分野
|
PHARMACOLOGY & PHARMACY
|
| リソース情報 |
| ヒト・動物細胞 |
L929 |
