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

Authors

• Soonkyu Chung, Department of Food Science and Human Nutrition, University of Florida, Gainesville, FLFollow
• Jonathan Mark Brown, Comparative Medicine Wake Forest University School of Medicine, Winston-Salem, NC
• Maria Boysen Sandberg, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, DK-5230, Denmark
• Michael McIntosh, Department of Nutrition, University of North Carolina at Greensboro, Greensboro, NC

Document Type

Article

Date of this Version

2005

Citation

J Lipid Res. 2005 May ; 46(5): 885–895.

Comments

Used by permission.

Abstract

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.