α-MSH and Foxc2 promote fatty acid oxidation through C/EBPβ negative transcription in mice adipose tissue.

α-MSH and Foxc2 promote fatty acid oxidation through C/EBPβ negative transcription in mice adipose tissue.
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α-MSH 和 Foxc2 通过小鼠脂肪​​组织中的 C/EBP β 负转录促进脂肪酸氧化

DOI:
10.1038/srep36661
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发表时间:
2016-11-07
期刊:
影响因子:
4.6
通讯作者:
Sun C
Sun C
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Gan L;Liu Z;Chen Y;Dan Luo;Feng F;Liu G;Sun C

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α 黑素细胞刺激激素 (α-MSH) 和叉头盒 C2 蛋白 (Foxc2) 增强多个组织中的脂肪分解。然而,它们在脂肪脂肪酸氧化(FAO)中的关系仍不清楚。在这里,我们证明 α-MSH 和 Foxc2 增加白色脂肪组织 (WAT) 和棕色脂肪组织 (BAT) 中棕榈酸酯氧化为 CO2。 α-MSH 和 Foxc2 降低了 C/EBPβ 表达。 α-MSH 和 pc-Foxc2 处理提高了 FFA 水平,同时白色和棕色脂肪细胞中的 FFA 也增加了。 α-MSH和pc-Foxc2组中FAO关键酶、中链酰基辅酶A脱氢酶(MCAD)和长链酰基辅酶A脱氢酶(LCAD)的表达增加。 α-MSH 和 Foxc2 联合处理通过增加 CPT-1 的活性和 ACC 的磷酸化来协同促进FAO。我们发现 C/EBPβ 与 MC5R 和 Foxc2 启动子区域结合并抑制FAO。 α-MSH和Foxc2单独治疗或联合治疗可增加cAMP水平。此外,cAMP/PKA 途径特异性抑制剂 (H89) 阻断了 FAO,尽管在 α-MSH 和 Foxc2 中均添加了组。而cAMP激动剂毛喉素则促进FAO并增强α-MSH和Foxc2的作用。总的来说,α-MSH和Foxc2通过cAMP/PKA信号通路在WAT和BAT中共同促进FAO。 C/EBPβ作为转录抑制因子抑制α-MSH和Foxc2的表达以及FAO。
Alpha melanocyte stimulating hormone (α-MSH) and Forkhead box C2 protein (Foxc2) enhance lipolysis in multiple tissues. However, their relationship in adipose fatty acid oxidation (FAO) remains unclear. Here, we demonstrated that α-MSH and Foxc2 increased palmitate oxidation to CO2 in white (WAT) and brown adipose tissue (BAT). C/EBPβ expression was reduced by α-MSH and Foxc2. FFA level was elevated by α-MSH and pc-Foxc2 treatment along with increased FAO in white and brown adipocytes. The expression of FAO key enzymes, medium-chain acyl-CoA dehydrogenase (MCAD) and long-chain acyl-CoA dehydrogenase (LCAD) were increased in α-MSH and pc-Foxc2 group. Combination of α-MSH and Foxc2 treatment synergistically promoted FAO through increasing the activity of CPT-1 and phosphorylation of ACC. We found C/EBPβ bind to MC5R and Foxc2 promoter regions and inhibited FAO. cAMP level was increased by α-MSH and Foxc2 individually treated or combined treatment. Furthermore, cAMP/PKA pathway-specific inhibitor (H89) blocked the FAO, despite in α-MSH and Foxc2 both added group. While forskolin, the cAMP agonist, promoted FAO and enhanced the effect of α-MSH and Foxc2. Collectively, α-MSH and Foxc2 mutual promote FAO in WAT and BAT via cAMP/PKA signal pathway. And C/EBPβ as a transcription suppressor inhibits α-MSH and Foxc2 expression and FAO.
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