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, Michael McIntosh

Research output: Contribution to journalArticle

69 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)885-895
Number of pages11
JournalJournal of Lipid Research
Volume46
Issue number5
DOIs
StatePublished - Dec 1 2005

Fingerprint

Lipolysis
Adipocytes
Lipids
Ribosomal Protein S6 Kinases
S 6
Proteins
Ribosomal Proteins
Sirolimus
Triglycerides
Cytosol
Perilipin-2
trans-10,cis-12-conjugated linoleic acid
Lipid Droplet Associated Proteins
Chemical activation
Messenger RNA
Perilipin-1
Metabolism

Keywords

  • Adipose differentiation-related protein
  • Conjugated linoleic acid
  • Mammalian target of rapamycin
  • Mitogen-activated protein kinase kinase/extracellular signal-related kinase signaling
  • Perilipin
  • Triglycerides

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Trans-10, cis-12 CLA increases adipocyte lipolysis and alters lipid droplet-associated proteins : Role of mTOR and ERK signaling. / Chung, Soonkyu; Brown, Jonathan Mark; Sandberg, Maria Boysen; McIntosh, Michael.

In: Journal of Lipid Research, Vol. 46, No. 5, 01.12.2005, p. 885-895.

Research output: Contribution to journalArticle

Chung, Soonkyu ; Brown, Jonathan Mark ; Sandberg, Maria Boysen ; McIntosh, Michael. / Trans-10, cis-12 CLA increases adipocyte lipolysis and alters lipid droplet-associated proteins : Role of mTOR and ERK signaling. In: Journal of Lipid Research. 2005 ; Vol. 46, No. 5. pp. 885-895.
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AB - 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.

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