Trans-10,cis-12 CLA increases adipocyte lipolysis and alters lipid droplet-associated proteins:: role of mTOR and ERK signaling

Lipid droplet-associated proteins play an important role in adipocyte triglyceride (TG) metabolism. Here, we show that trans - 10, cis - 12 conjugated 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-induced increase 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 of small lipid droplets, displacing perilipin. Intriguingly, trans - 10, cis - 12 CLA increased ADRP protein expression to a much greater extent than ADRP mRNA without affecting stability, suggesting translational control of ADRP. To this end, we found that trans - 10, cis - 12 CLA increased activation of the mammalian target of rapamycin/p70 S6 ribosomal protein kinase/S6 ribosomal protein (mTOR/p70S6K/ S6) pathway. Collectively, these data demonstrate that the trans - 10, cis - 12 CLA-mediated reduction of human adipocyte TG content is associated with the differential localization and expression of lipid droplet-associated proteins. This process involves both the translational control of ADRP through the activation of mTOR/p70S6K/ S6 signaling and transcriptional control of perilipin A.