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.
Chung
Soonkyu
S
Department of Nutrition, University of North Carolina at Greensboro, Greensboro, NC 27402-6170, USA.
Brown
Jonathan Mark
JM
Sandberg
Maria Boysen
MB
McIntosh
Michael
M
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
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
Am J Physiol Endocrinol Metab. 2003 Feb;284(2):E322-30
12388166
Biochim Biophys Acta. 2000 Jan 17;1483(2):251-62
10634941
Nat Genet. 2000 Dec;26(4):474-9
11101849
Genes Dev. 2004 Aug 15;18(16):1926-45
15314020
J Biol Chem. 2004 Nov 5;279(45):47066-75
15337759
J Nutr. 2002 Oct;132(10):3105-12
12368402
Diabetes. 2004 May;53(5):1261-70
15111495
Cell Tissue Res. 1998 Nov;294(2):309-21
9799447
Biochim Biophys Acta. 2000 Nov 15;1488(3):245-54
11082534
J Lipid Res. 1997 Nov;38(11):2249-63
9392423
Diabetes Care. 2002 Sep;25(9):1516-21
12196420
J Nutr Biochem. 2002 Sep;13(9):508
12231420
Biochem Soc Trans. 2003 Dec;31(Pt 6):1120-4
14641008
J Biol Chem. 2000 Feb 18;275(7):5011-5
10671541
J Biol Chem. 2001 Nov 30;276(48):45456-61
11581251
Lipids. 1999 Mar;34(3):243-8
10230717
Lipids. 1997 Aug;32(8):853-8
9270977
Am J Physiol. 1999 Apr;276(4 Pt 2):R1172-9
10198400
J Biol Chem. 1999 Jun 11;274(24):16825-30
10358026
Diabetes. 2002 Dec;51(12):3368-75
12453888
J Biol Chem. 2000 Dec 8;275(49):38486-93
10948207
Nat Med. 2002 Oct;8(10):1122-8
12357248
J Nutr. 2003 Oct;133(10):3041-6
14519781
Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11477-81
7972087
J Lipid Res. 2003 Jul;44(7):1287-300
12730300
J Nutr. 1999 Nov;129(11):2037-42
10539781
Carcinogenesis. 1987 Dec;8(12):1881-7
3119246
J Biol Chem. 2004 Jun 18;279(25):26735-47
15067015
J Nutr. 2000 Dec;130(12):2943-8
11110851
Diabetes. 2002 Oct;51(10):2929-35
12351429
J Nutr. 2001 Sep;131(9):2316-21
11533273
J Biol Chem. 1998 Sep 18;273(38):24665-9
9733764
J Nutr. 2002 Oct;132(10):2995-8
12368384
J Int Med Res. 2001 Sep-Oct;29(5):392-6
11725826
J Cell Physiol. 2000 Feb;182(2):297-302
10623894
J Biol Chem. 2004 Sep 24;279(39):40683-9
15220344
J Cell Biol. 2003 Jun 23;161(6):1093-103
12810697
Genes Dev. 2001 Apr 1;15(7):807-26
11297505
Biochem J. 2004 Feb 15;378(Pt 1):73-82
14629199
Science. 2004 Nov 19;306(5700):1383-6
15550674
Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):7856-60
1518805
Semin Cell Dev Biol. 1999 Feb;10(1):51-8
10355028
Am J Physiol Endocrinol Metab. 2002 Oct;283(4):E775-83
12217895
Diabetes. 2004 May;53(5):1243-52
15111493
Biochem Biophys Res Commun. 2004 Jan 9;313(2):443-6
14684182
Lipids. 1999 Mar;34(3):235-41
10230716
Proc Natl Acad Sci U S A. 2001 May 22;98(11):6494-9
11371650