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 (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.