期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 365, 期 2, 页码 260-269出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2012.10.030
关键词
Cyclosporin A; Tacrolimus; Rapamycin; Lipolysis; Adipocytes; Lipid storage
资金
- Portuguese Foundation for Science and Technology [SFRH/BD/41044/2007, PTDC/SAU-OSM/104124/2008]
- University of Gothenburg/Sahlgrenska University Hospital [LUA/ALF ALFGBG-11379]
- AstraZeneca RD
- Regional FoU [VGFOUREG-12052]
- Swedish Heart and Lung Foundation, Sweden [20100648]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/41044/2007] Funding Source: FCT
Cyclosporin A (CsA), tacrolimus and rapamycin are immunosuppressive agents (IAs) associated with insulin resistance and dyslipidemia, although their molecular effects on lipid metabolism in adipose tissue are unknown. We explored IAs effects on lipolysis, lipid storage and expression of genes involved on lipid metabolism in isolated human adipocytes and/or adipose tissue obtained via subcutaneous and omental fat biopsies. CsA, tacrolimus and rapamycin increased isoproterenol-stimulated lipolysis and inhibited lipid storage by 20-35% and enhanced isoproterenol-stimulated hormone-sensitive lipase Ser552 phosphorylation. Rapamycin also increased basal lipolysis (similar to 20%) and impaired insulin's antilipolytic effect. Rapamycin, down-regulated the gene expression of perilipin, sterol regulatory element-binding protein 1 (SREBP1) and lipin 1, while tacrolimus down-regulated CD36 and aP2 gene expression. All three IAs increased IL-6 gene expression and secretion, but not expression and secretion of TNF-alpha or adiponectin. These findings suggest that CsA, tacrolimus and rapamycin enhance lipolysis, inhibit lipid storage and expression of lipogenic genes in adipose tissue, which may contribute to the development of dyslipidemia and insulin resistance associated with immunosuppressive therapy. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据