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靶向 PLIN2/PLIN5-PPARγ:莱菔硫烷扰乱脂滴的成熟。

Targeting PLIN2/PLIN5-PPARγ: Sulforaphane Disturbs the Maturation of Lipid Droplets.

机构信息

School of Public Health and Management, Wenzhou Medical University, Wenzhou, 325035, China.

Department of Food Science and Engineering, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, China.

出版信息

Mol Nutr Food Res. 2019 Oct;63(20):e1900183. doi: 10.1002/mnfr.201900183. Epub 2019 Jul 30.

DOI:10.1002/mnfr.201900183
PMID:31325205
Abstract

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 (PPARγ) induces the accumulation of TAG and the up-regulation of PLIN2 and PLIN5, which are not reversed by SFN. These results suggest that PPARγ 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 PPARγ.

摘要

范围

尽管众所周知,萝卜硫素 (SFN) 有益于改善脂质代谢紊乱,但 SFN 对脂滴 (LD)——游离脂肪酸和甾醇作为三酰基甘油 (TAG) 和胆固醇酯 (CE) 的储存单元——成熟的影响仍远未被理解。

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 可减少 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,SFN 可降低 LD 相关蛋白 PLIN2 和 PLIN5 的表达,无论是在体内还是体外,但不降低 PLIN1 和 PLIN3 的表达。此外,过氧化物酶体增殖物激活受体 γ (PPARγ) 的过表达会导致 TAG 的积累和 PLIN2 和 PLIN5 的上调,而 SFN 并不能逆转这些作用。这些结果表明,PPARγ 可能是 SFN 在脂质代谢中的靶点。

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 PPARγ 降低 PLIN2 和 PLIN5。

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