Targeting PLIN2/PLIN5-PPARγ: Sulforaphane Disturbs the Maturation of Lipid Droplets
Targeting PLIN2/PLIN5-PPARγ: Sulforaphane Disturbs the Maturation of Lipid Droplets
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靶向 PLIN2/PLIN5-PPARγ：SFN 干扰脂滴的成熟
DOI：
10.1002/mnfr.201900183
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发表时间：
2019-07-30
影响因子：
5.2
通讯作者：
Shan, Yujuan
中科院分区：
文献类型：
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作者：
Tian, Sicong;Lei, Peng;Shan, Yujuan
范围 萝卜硫素 (SFN) 对脂滴 (LD) 成熟的影响尚不清楚，脂滴 (LD) 是游离脂肪酸和甾醇（如三酰甘油酯 (TAG) 和胆固醇酯 (CE) 的储存单位），尽管已知 SFN 有益于改善脂质代谢紊乱。方法和结果在HHL-5肝细胞和啮齿动物中建立高脂肪摄入模型。 SFN 减少了 LD 的数量和大小。脂质核心成分 (TAG 和 CE) 的积累减少，其关键合成酶酰基辅酶 A：二酰基甘油酰基转移酶 2 (DGAT2) 和酰基辅酶 A：胆固醇酰基转移酶 1 (ACAT1) 的表达也受到抑制。此外，无论在体内还是体外，SFN 都会降低 LD 相关蛋白 PLIN2 和 PLIN5 的表达，但不会降低 PLIN1 和 PLIN3 的表达。此外，过氧化物酶体增殖物激活受体γ（PPARγ）的过度表达会诱导TAG的积累以及PLIN2和PLIN5的上调，而SFN不会逆转这种情况。这些结果表明 PPAR γ 可能是 SFN 在脂质代谢中的靶标。结论 SFN 通过抑制中性脂质核心的形成来干扰 LD 成熟，并通过下调 PPAR gamma 来减少 PLIN2 和 PLIN5。
Scope The effects of sulforaphane (SFN) on the maturation of lipid droplets (LDs)-the storage units for free fatty acids and sterols as triacylglycerides (TAG) and cholesterol esters (CE)-are far from being understood, despite the fact that SFN is known to be beneficial for ameliorating lipid metabolism disorders. Methods and Results High-fat-intake models are established in both HHL-5 hepatocytes and rodents. The numbers and sizes of LDs are decreased by SFN. The accumulation of lipid core components (TAG & CE) is reduced and the expression of their key synthetases, acyl-coenzyme A: diacylglycerol acyltransferases 2 (DGAT2) and acyl-coenzyme A: cholesterol acyltransferases 1 (ACAT1), is also inhibited. Moreover, SFN decreases LD-associated protein PLIN2 and PLIN5 expression, but not that of PLIN1 and PLIN3, both in vivo and in vitro. Furthermore, over-expression of peroxisome proliferator-activated receptor gamma (PPAR gamma) induces the accumulation of TAG and the up-regulation of PLIN2 and PLIN5, which are not reversed by SFN. These results suggest that PPAR gamma may be a target of SFN in lipid metabolism. Conclusion SFN disturbs LD maturation by inhibiting the formation of the neutral lipid core and decreases PLIN2 and PLIN5 via down-regulation of PPAR gamma.