出版社：American Society for Biochemistry and Molecular Biology
摘要：Lipid droplet-associated proteins play an important role inadipocyte triglyceride (TG) metabolism. Here, we show that trans-10,cis-12conjugated linoleic acid (CLA), but not cis-9,trans-11 CLA,increased lipolysis and altered human adipocyte lipid droplet morphology.Before this change in morphology, there was a rapid trans-10,cis-12 CLA-inducedincrease in the accumulation of perilipin A in the cytosol,followed by the disappearance of perilipin A protein. In contrast,protein levels of adipose differentiation-related protein (ADRP)were increased in cultures treated with trans-10,cis-12 CLA.Immunostaining revealed that ADRP localized to the surface ofsmall lipid droplets, displacing perilipin. Intriguingly, trans-10,cis-12CLA increased ADRP protein expression to a much greater extentthan ADRP mRNA without affecting stability, suggesting translationalcontrol of ADRP. To this end, we found that trans-10,cis-12CLA increased activation of the mammalian target of rapamycin/p70S6 ribosomal protein kinase/S6 ribosomal protein (mTOR/p70S6K/S6) pathway.
Collectively, these data demonstrate that the trans-10,cis-12 CLA-mediatedreduction of human adipocyte TG content is associated with thedifferential localization and expression of lipid droplet-associatedproteins. This process involves both the translational controlof ADRP through the activation of mTOR/p70S6K/S6 signaling andtranscriptional control of perilipin A.Abbreviations: ADRP, adipose differentiation-related protein; CLA, conjugated linoleic acid; ERK, extracellular signal-related kinase; GPCR, G protein-coupled receptor; HSL, hormone-sensitive lipase; MEK, mitogen-activated protein kinase kinase; mTOR, mammalian target of rapamycin; PKA, protein kinase A; p70S6K, p70 S6 ribosomal protein kinase; S6, S6 ribosomal protein; SV, stromal vascular; TG, triglyceride; TNF-, tumor necrosis factor-; UTR, untranslated region; 5'-TOP, 5'-terminal oligopyrimidine
Supplementary key words conjugated linoleic acid • perilipin • adipose differentiation-related protein • triglycerides • mammalian target of rapamycin • mitogen-activated protein kinase kinase/extracellular signal-related kinase signaling
, tumor necrosis factor-
