マウス褐色および白色脂肪細胞におけるレプチン分泌とレプチンmRNA発現に及ぼすアンジオテンシンIIの作用

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Although it has been implied that the renin/angiotensin system is deeply involved in the regulation of adipocyte function, the details of the role of the system remain to be elucidated. In the present study, we investigated the effects of angiotensin II (Ang II) on leptin secretion and leptin mRNA expression in the adipocytes of brown adipose tissues (BAT) and white adipose tissues (WAT) of mice. Mature adipocytes were prepared by collagenase treatment and culture in DMEM containing 10% fetal bovine serum and 4 nM insulin. Cultured adipocytes were incubated in the medium containing Ang II (10^<-9>～10^<-11>M),the AT1-selective antagonist Losartan (10^<-6>～10^<-8>M), or the AT2-selective antagonist PD 123319 (10^<-6>～10^<-8>M) alone, or a combination of Ang II and antagonist. After incubation for 24 hr, the leptin concentration in the medium was determined by radioimmunoassay. Leptin mRNA expression in the cells was determined by RT-PCR. Ang II increased and decreased leptin secretion by BAT and WAT, respectively, in a dose-dependent manner. Ang II did not affect leptin mRNA expression in BAT, but it significantly decreased leptin mRNA expression in WAT. The effect of Ang II on leptin secretion by BAT was significantly suppressed by PD123319 and the effect of Ang II on leptin secretion and leptin mRNA expression in WAT was suppressed by Losartan. These results suggested that Ang II is involved in the regulation of adipose tissue function through its effects on leptin synthesis and/or secretion. In addition, since the effects in BAT and WAT were mediated through different Ang II receptor subtypes, AT2 in BAT and AT1 in WAT, it is suggested that the receptor subtype is of great biological significance in the action of Ang II on adipocytes as well as on the cardiovascular system.
東京女子医科大学の論文
2000-03-25

マウス褐色および白色脂肪細胞におけるレプチン分泌とレプチンmRNA発現に及ぼすアンジオテンシンIIの作用

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