17β-estradiol lowers triglycerides in adipocytes via estrogen receptor α and it may be attenuated by inflammation.

17β-estradiol lowers triglycerides in adipocytes via estrogen receptor α and it may be attenuated by inflammation.
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17β-雌二醇通过雌激素受体α降低脂肪细胞中的甘油三酯,并且可能会因炎症而减弱

DOI:
10.1186/s12944-017-0575-6
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发表时间:
2017-09-25
影响因子:
4.5
通讯作者:
Li XP
Li XP
中科院分区:
医学3区
文献类型:
--
作者:
Luo F;Huang WY;Guo Y;Ruan GY;Peng R;Li XP

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据报道,雌激素可以预防肥胖,但其机制尚不清楚。本研究旨在探讨17-β-雌二醇(17-β-E_2)在脂多糖刺激下对脂肪细胞甘油三酯代谢的影响,为雌激素的作用提供新的可能机制。3T3-L1脂肪细胞体外培养并分化为成熟脂肪细胞。将分化的3T3-L1细胞分为6组:(1)对照组,仅用0.1%二甲基亚砜处理;(2)17β-E2组,用1、0.1或0.001μM 17β-E_2处理48h;(3)17β-E_2+MPP组,用10μM mMPP(选择性ERα受体抑制剂)处理1h,再与1μM 17β-E_2孵育48h;(4)17β-E_2+PHTPP组,用10μM PHTPP(一种选择性ERβ受体拮抗剂)预处理,然后与1μM 17β-E_2孵育48 h,(V)内毒素组,用100 ng/mLLPS预处理24 h,然后用PBS洗涤3次,单独用0.1%二甲基亚砜孵育48 h;(6)17β-E_2+脂多糖组,用100 ng/mLLPS处理24 h后,用硫代巴比妥钠洗涤细胞3次,再用1μM 17β-E_2孵育48 h,测定分化后3T3-L1细胞的甘油三酯和脂肪甘油三酯脂肪酶水平及培养上清液中白介素6的浓度。与对照组相比,1μM和0.1μM 17β-E2使细胞内甘油三酯水平分别降低约20%和10%(P均<0.0 5)。17β-E2对分化的3T3-L1细胞的降甘油三酯作用可被ERα拮抗剂MPP所阻断,但不能被ERβ拮抗剂PHTPP所阻断。与对照组相比,内毒素组和17β-E_2+内毒素组诱导分化的3T3-L1细胞培养上清液中IL-6水平显著升高(P均<0.05)。内毒素组和17β-E_2+内毒素组IL-6水平无明显差异(P>0.05)。对照组、脂多糖组和17β-E_2+脂多糖组分化后的3T3-L1细胞甘油三酯含量差异无统计学意义(P均>0.05)。17β-E_2组ATGL表达明显高于对照组(P<0.05),ER-α拮抗剂MPP或脂多糖可抑制其表达。17β-E_2通过雌激素α增加脂肪细胞ATGL的表达,降低甘油三酯的表达,但对脂多糖刺激的脂肪细胞无明显影响。
Estrogen was reported to protect against obesity, however the mechanism remains unclear. We aimed to investigate the impact of 17β-estradiol (17β-E2) on triglyceride metabolism in adipocytes with or without lipopolysacchride (LPS) stimulating, providing novel potential mechanism for estrogen action. 3T3-L1 adipocytes were cultured and differentiated into mature adipocytes in vitro. The differentiated 3T3-L1 cells were divided into six groups: (i) control group, treated with 0.1% DMSO alone; (ii) 17β-E2 group, treated with 1, 0.1, or 0.001 μM 17β-E2 for 48 h; (iii) 17β-E2 plus MPP group, pre-treated with 10 μM MPP (a selective ERα receptor inhibitor) for 1 h, then incubated with 1 μM 17β-E2 for 48 h; (iv) 17β-E2 plus PHTPP group, pre-treated with 10 μM PHTPP (a selective ERβ receptor inhibitor), then incubated with 1 μM 17β-E2 for 48 h; (v) LPS group, pre-treated with 100 ng/mL LPS for 24 h, then cells were washed by PBS for 3 times and incubated with 0.1% DMSO alone for 48 h; (vi) 17β-E2 plus LPS group, pre-treated with 100 ng/mL LPS for 24 h, then cells were washed by PBS for 3 times and incubated with 1 μM 17β-E2 for 48 h. The levels of triglyceride and adipose triglyceride lipase (ATGL) in differentiated 3T3-L1 cells and the concentrations of interleukin-6 (IL-6) in culture medium were measured. Comparing with control group, 1 μM and 0.1 μM 17β-E2 decreased the intracellular TG levels by about 20% and 10% respectively (all P < 0.05). The triglyceride-lowing effect of 17β-E2 in differentiated 3T3-L1 cells was abolished by ERα antagonist MPP but not ERβ antagonist PHTPP. Comparing with control group, the IL-6 levels were significantly higher in the culture medium of the cultured differentiated 3T3-L1 cells in LPS group and 17β-E2 + LPS group (all P < 0.05). And, the IL-6 levels were similar in LPS group and 17β-E2 + LPS group (P > 0.05). There was no significant difference in the triglyceride contents of differentiated 3T3-L1 cells among control group, LPS group and 17β-E2 + LPS group (all P > 0.05). ATGL expression in 17β-E2 group was significantly higher than control group (P < 0.05), which was abolished by ERα antagonist MPP or LPS. 17β-E2 increased ATGL expression and lowered triglycerides in adipocytes but not in LPS stimulated adipocytes via estrogen ERα.
DOI: 10.1038/nrcardio.2016.185
发表时间: 2017-03
期刊: Nature reviews. Cardiology
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期刊: ENDOCRINOLOGY
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雌激素通过调节肝脏 APOA5 表达降低甘油三酯
DOI: 10.1186/s12944-017-0463-0
发表时间: 2017-04-04
影响因子: 4.5
作者:
Luo F;Guo Y;Ruan GY;Peng R;Li XP
通讯作者: Li XP