POSTTRANSLATIONAL REGULATION OF PERILIPIN EXPRESSION - STABILIZATION BY STORED INTRACELLULAR NEUTRAL LIPIDS

The perilipins are a family of polyphosphorylated proteins found exclu sively surrounding neutral lipid storage droplets in adipocytes and st eroidogenic cells, In steroidogenic cells, the cholesterol ester-rich lipid storage droplets are encoated with perilipins A and C. This stud y describes the dependence of perilipin levels on neutral lipid storag e in cultured Y-1 adrenal cortical cells, The addition of fatty acids and cholesterol to the culture medium of Y-1 adrenal cortical cells gr eatly increased the storage of cholesterol esters and triacylglycerols concomitant with the formation of many new lipid storage droplets, Th e addition of fatty acids to the culture medium also produced a transi ent 6-fold increase in levels of perilipin A, but not C, mRNA, while m uch larger and stable increases in both perilipin A and C proteins wer e observed, The increases in perilipin protein levels were dependent u pon the metabolism of fatty acids to triacylglycerol or cholesterol es ters, since the incubation of cells with bromopalmitate, a poorly meta bolized fatty acid, failed to yield large increases in lipid content o r perilipin levels, Constitutive expression of epitope-tagged perilipi ns in transfected Y-1 adrenal cortical cells was regulated by lipid si milarly to expression of the endogenous perilipins despite an absence of untranslated perilipin mRNA sequences in the expression constructs. Epitope-tagged perilipin A mRNAs were efficiently loaded with polyrib osomes whether or not fatty acids were added to the culture medium; th erefore, the increase in perilipin levels in the presence of fatty aci ds is likely due to factors other than increased translational efficie ncy, We suggest that the large increase in cellular perilipin levels u pon lipid loading of cells is the result of post-translational stabili zation of newly synthesized perilipins by stored neutral lipids.