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

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.