Inhibition of leptin release by atrial natriuretic peptide (ANP) in human adipocytes
Inhibition of leptin release by atrial natriuretic peptide (ANP) in human adipocytes
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DOI：
10.1016/s0006-2952(03)00154-0
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发表时间：
2003-06-01
影响因子：
5.8
通讯作者：
Hiler, ML
中科院分区：
文献类型：
--
作者：
Fain, JN;Kanu, A;Hiler, ML
将心房利钠肽（ANP）添加到原代培养中分离的人类脂肪细胞中，在孵育24或48小时后，可抑制瘦素的释放。异丙肾上腺素（ISO）对瘦素释放的抑制作用也被胰岛素部分逆转，而ANP对瘦素释放的抑制作用则不受影响。N-[2-（p -溴肉桂胺）乙基]-5-异喹啉磺胺（H-89）也有类似的结果，这是一种蛋白激酶a的细胞渗透性抑制剂。H-89显著降低了ISO对脂肪分解和瘦素释放的影响，而不影响由于ANR引起的脂肪分解的刺激或瘦素释放的抑制。使用N-omega-硝基- l-精氨酸抑制内源性一氧化氮形成导致瘦素释放增加20%。提示一氧化氮/环GMP通路可能在调节内源性瘦素释放中起一定作用。同样，将一氧化氮供体(Z)-1-（2-氨基乙基）- n-（2-氨基乙基）重氮-1-ium-1,2- diazen-1-（2-氨基乙基）（DETA NONOate）以0.1或1mum添加到人体脂肪组织外植体中，可使脂肪分解提高29%。我们的数据表明，ANP的溶脂作用可能是继发于刺激人脂肪细胞中循环GMP的积累，这伴随着瘦素释放的抑制。(C) 2003爱思唯尔科学有限公司版权所有。
The addition of atrial natriuretic peptide (ANP) to isolated human adipocytes in primary culture from very obese individuals resulted in an inhibition of leptin release after a 24- or 48-hr incubation. There was also an inhibition of leptin release by isoproterenol (ISO) that was partially reversed by insulin, whereas the inhibition due to ANP was unaffected. Similar results were seen with N-[2-(P-bromocinnamylamino)ethyl]-5-isoquinolinesulphonamide (H-89), which is a cell-permeable inhibitor of protein kinase A. H-89 markedly reduced the effects of ISO on both lipolysis and leptin release without affecting the stimulation of lipolysis or the inhibition of leptin release due to ANR Inhibition of endogenous nitric oxide formation using N-omega-nitro-L-arginine resulted in a 20% increase in leptin release over 48 hr, which suggests that the nitric oxide/cyclic GMP pathway might play a small role in the regulation of endogenous leptin release. Similarly, the addition of the nitric oxide donor (Z)-1-(2-aminoethyl)-N-(2-aminoethyl)diazen-1-ium-1,2-diolate (DETA NONOate) at 0.1 or I muM to explants of human adipose tissue enhanced lipolysis by 29%. Our data demonstrate that the lipolytic effect of ANP is probably secondary to stimulation of cyclic GMP accumulation in human adipocytes, and this is accompanied by an inhibition of leptin release. (C) 2003 Elsevier Science Inc. All rights reserved.