Glucocorticoids antagonize tumor necrosis factor-α-stimulated lipolysis and resistance to the antilipolytic effect of insulin in human adipocytes
Glucocorticoids antagonize tumor necrosis factor-α-stimulated lipolysis and resistance to the antilipolytic effect of insulin in human adipocytes
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DOI：
10.1152/ajpendo.00228.2012
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发表时间：
2012-11-01
影响因子：
5.1
通讯作者：
Fried, Susan K.
中科院分区：
文献类型：
--
作者：
Lee, Mi-Jeong;Fried, Susan K.
李俊杰，Fried SK.糖皮质激素拮抗肿瘤坏死因子α刺激的脂肪分解和对胰岛素抗脂肪分解作用的抵抗。[J] .中国生物医学工程学报，2016,31(2):444 - 444。2012年9月4日首次发表；doi: 10.1152 / ajpendo.00228.2012。-肥胖脂肪组织中高浓度的肿瘤坏死因子增加基础脂肪分解并拮抗胰岛素信号。肥胖的脂肪细胞也暴露于高水平的糖皮质激素（GCs），它在许多细胞类型中拮抗TNF的作用。我们检验了TNF降低对胰岛素抗脂溶作用敏感性的假设，而GCs在分化的人类脂肪细胞中拮抗这种作用。在用TNF、地塞米松（DEX）或DEX + TNF处理脂肪细胞长达48小时后，测量脂溶和脂溶蛋白的表达水平。TNF不仅增加了基础脂溶，而且在人脂肪细胞中引起对胰岛素抗脂溶作用的抵抗。DEX单独对脂肪溶解无显著影响。通过拮抗肿瘤坏死因子刺激pka介导的激素敏感脂肪酶（HSL）丝氨酸（563）和丝氨酸（660）和佩里平的磷酸化，DEX联合治疗阻断了肿瘤坏死因子诱导的基础脂肪分解和胰岛素抵抗。TNF不影响perilipin、HSL或磷酸二酯酶- 3b的质量，但矛盾的是，它抑制了脂肪组织甘油三酯脂肪酶的表达，而这种作用被DEX阻断了。GCs能够在一定程度上抑制TNF的脂溶作用，这可能既减少了过量脂溶的潜在有害影响，又有助于肥胖中的脂肪积累。
Lee MJ, Fried SK. Glucocorticoids antagonize tumor necrosis factor-alpha-stimulated lipolysis and resistance to the antilipolytic effect of insulin in human adipocytes. Am J Physiol Endocrinol Metab 303: E1126-E1133, 2012. First published September 4, 2012; doi:10.1152/ajpendo.00228.2012.-High concentrations of TNF within obese adipose tissue increase basal lipolysis and antagonize insulin signaling. Adipocytes of the obese are also exposed to elevated levels of glucocorticoids (GCs), which antagonize TNF actions in many cell types. We tested the hypothesis that TNF decreases sensitivity to the antilipolytic effect of insulin and that GCs antagonize this effect in differentiated human adipocytes. Lipolysis and expression levels of lipolytic proteins were measured after treating adipocytes with TNF, dexamethasone (DEX), or DEX + TNF for up to 48 h. TNF not only increased basal lipolysis, it caused resistance to the antilipolytic effects of insulin in human adipocytes. DEX alone did not significantly affect lipolysis. Cotreatment with DEX blocked TNF induction of basal lipolysis and insulin resistance by antagonizing TNF stimulation of PKA-mediated phosphorylation of hormone-sensitive lipase (HSL) at Ser(563) and Ser(660) and perilipin. TNF did not affect perilipin, HSL, or phosphodiesterase-3B mass but paradoxically suppressed adipose tissue triglyceride lipase expression, and this effect was blocked by DEX. The extent to which GCs can restrain the lipolytic actions of TNF may both diminish the potentially deleterious effects of excess lipolysis and contribute to fat accumulation in obesity.