Regulation of lipogenesis by glucocorticoids and insulin in human adipose tissue.
Regulation of lipogenesis by glucocorticoids and insulin in human adipose tissue.
复制标题
DOI：
10.1371/journal.pone.0026223
复制
发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Tomlinson JW
中科院分区：
文献类型：
--
作者：
Gathercole LL;Morgan SA;Bujalska IJ;Hauton D;Stewart PM;Tomlinson JW
糖皮质激素（GC）过量的患者，即库欣综合征，发展为以向心性肥胖和胰岛素抵抗为特征的典型表型。已知GC通过刺激脂解增加脂肪酸从脂肪中的释放，然而，GC对调节脂质积累的过程的影响尚未被探索。活性GC的细胞内水平取决于11β-羟基类固醇脱氢酶1型（11β-HSD 1）的活性，我们假设11β-HSD 1活性可以调节人脂肪组织（Chub-S7细胞系和人皮下（sc）和网膜（om）脂肪细胞的原代培养物）中的脂质稳态。在脂肪细胞分化过程中，脂肪生成增加，而β-氧化减少。GC处理降低脂肪生成，但不改变Chub-S7细胞中的β-氧化速率，而胰岛素在所有脂肪细胞模型中增加脂肪生成。Chub-S7细胞的低剂量地塞米松预处理（5 nM）增强了胰岛素刺激脂肪生成的能力，并且在原代sc细胞中没有脂肪组织胰岛素抵抗的证据。皮质醇和可的松均降低脂肪生成;选择性11β-HSD 1抑制完全消除可的松介导的脂肪生成抑制。GC对脂质体内平衡具有强有力的作用，这些作用依赖于与胰岛素的相互作用。这些体外数据表明，通过选择性抑制11β-HSD 1来操纵GC的可用性可以改变人脂肪细胞中的脂质稳态。
Patients with glucocorticoid (GC) excess, Cushing's syndrome, develop a classic phenotype characterized by central obesity and insulin resistance. GCs are known to increase the release of fatty acids from adipose, by stimulating lipolysis, however, the impact of GCs on the processes that regulate lipid accumulation has not been explored. Intracellular levels of active GC are dependent upon the activity of 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) and we have hypothesized that 11β-HSD1 activity can regulate lipid homeostasis in human adipose tissue (Chub-S7 cell line and primary cultures of human subcutaneous (sc) and omental (om) adipocytes. Across adipocyte differentiation, lipogenesis increased whilst β-oxidation decreased. GC treatment decreased lipogenesis but did not alter rates of β-oxidation in Chub-S7 cells, whilst insulin increased lipogenesis in all adipocyte cell models. Low dose Dexamethasone pre-treatment (5 nM) of Chub-S7 cells augmented the ability of insulin to stimulate lipogenesis and there was no evidence of adipose tissue insulin resistance in primary sc cells. Both cortisol and cortisone decreased lipogenesis; selective 11β-HSD1 inhibition completely abolished cortisone-mediated repression of lipogenesis. GCs have potent actions upon lipid homeostasis and these effects are dependent upon interactions with insulin. These in vitro data suggest that manipulation of GC availability through selective 11β-HSD1 inhibition modifies lipid homeostasis in human adipocytes.
登录
查看更多内容
影响因子：
158.5
作者：
Calle, EE;Thun, MJ;Heath, CW
通讯作者：
Heath, CW
DOI：
10.1210/jc.2008-1297
发表时间：
2008-12
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
Kola B;Christ-Crain M;Lolli F;Arnaldi G;Giacchetti G;Boscaro M;Grossman AB;Korbonits M
通讯作者：
Korbonits M
影响因子：
4.1
作者：
JAMDAR, SC
通讯作者：
JAMDAR, SC
影响因子：
15.9
作者：
FRIED, SK;RUSSELL, CD;BROLIN, RE
通讯作者：
BROLIN, RE
影响因子：
2.2
作者：
Lundgren, M.;Buren, J.;Eriksson, J. W.
通讯作者：
Eriksson, J. W.