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Journal of Lipid Research, Vol. 46, 885-895, May 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

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

Soonkyu Chung^*, Jonathan Mark Brown, Maria Boysen Sandberg and Michael McIntosh^1,*

^* Department of Nutrition, University of North Carolina at Greensboro, Greensboro, NC 27402-6170
Department of Pathology and Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157
Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, DK-5230, Denmark

¹ To whom correspondence should be addressed. e-mail: mkmcinto{at}uncg.edu

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.

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

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