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Antiobese function of platelet‐activating factor: increased adiposity in platelet‐activating factor receptor‐deficient mice with age
Author(s) -
Sugatani Junko,
Sadamitsu Satoshi,
Yamaguchi Masahiko,
Yamazaki Yasuhiro,
Higa Ryoko,
Hattori Yoshiki,
Uchida Takahiro,
Ikari Akira,
Sugiyama Wataru,
Watanabe Tatsuo,
Ishii Satoshi,
Miwa Masao,
Shimizu Takao
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.13-233262
Subject(s) - medicine , endocrinology , brown adipose tissue , platelet activating factor receptor , receptor , platelet activating factor , thermogenin , adipose tissue , chemistry , agonist , platelet , stimulation , catabolism , biology , metabolism , antagonist
Platelet‐activating factor receptor (PAFR)‐deficient mice developed a more severe obese state characterized by higher body mass (~25%) and epididymal fat mass (~55%) with age than that of wild‐type (WT) littermates. PAFR‐deficient mice did not show changes in the expression of critical genes involved in anabolic and catabolic metabolism in adipose, liver, and muscle tissues between 6 and 36 wk. However, a 38–81% reduction in β 3 /β 1 ‐adrenergic receptor (AR) and uncoupling protein 1 (UCP1) mRNA and protein levels was observed in the interscapular brown adipose tissue (BAT) of PAFR‐deficient mice. Whereas a single injection of the β 3 ‐adrenergic agonist, CL‐316,243 (25 μg/kg) increased temperatures in the brown fat and rectums of WT mice, this increase in temperature was markedly suppressed in PAFR‐deficient mice. Acetyl‐CoA:lyso‐platelet‐activating factor (PAF) acetyltransferase, which is involved in PAF biosynthesis, and the PAF receptor were predominantly localized in BAT macrophages, whereas brown adipocytes possessed the enzyme and functional PAF receptors. The stimulation of brown adipocytes by PAF induced the expression of β 3 ‐AR mRNA and protein (1.5‐ and 1.9‐fold, respectively), but not that of UCP1. These results indicate that obesity in PAFR‐deficient mice resulted from impaired BAT activity and suggest that the antiobese function of PAF occurs through β 3 ‐AR/UCP1 expression in BAT.—Sugatani, J., Sadamitsu, S., Yamaguchi, M., Yamazaki, Y., Higa, R., Hattori, Y., Uchida, T., Ikari, A., Sugiyama, W., Watanabe, T., Ishii, S., Miwa, M., Shimizu, T. Antiobese function of platelet‐activating factor: increased adiposity in platelet‐activating factor receptor‐deficient mice with age. FASEB J . 28, 440–452 (2014). www.fasebj.org