title: Trans-10,cis-12 CLA increases adipocyte lipolysis and alters lipid droplet-associated proteins: role of mTOR and ERK signaling.
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.
authors.affiliation: Department of Nutrition, University of North Carolina at Greensboro, Greensboro, NC 27402-6170, USA.
authors.forename: Soonkyu
authors.initials: S
authors.lastname: Chung
authors.forename: Jonathan Mark
authors.initials: JM
authors.lastname: Brown
authors.forename: Maria Boysen
authors.initials: MB
authors.lastname: Sandberg
authors.forename: Michael
authors.initials: M
authors.lastname: McIntosh
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002352:Carrier Proteins; D017931:DNA Primers; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008066:Lipolysis; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D000070778:Perilipin-1; D000070780:Perilipin-2; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; D044243:Linoleic Acids, Conjugated; D008565:Membrane Proteins; C000602982:PLIN2 protein, human; D000070778:Perilipin-1; D000070780:Perilipin-2; D010750:Phosphoproteins; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D020123:Sirolimus
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