Lagathu, C., Bastard, J., Auclair, M., Maachi, M., Capeau, J. and Caron, M. (2003) Chronic interleukin-6 (IL-6) treatment increased IL-6 secretion and induced insulin resistance in adipocyte: prevention <strong>by</strong> rosiglitazone. Biophys. Biochem. Res. Commun. 311:372-379. Landos, C., Brasaemle, D., Schultz, C, Segrest, J., and Kimmel, A. (1999) Perilipins, ADRP, and other proteins that associate with intracellular lipids droplets in animal cells. Cell and Dev. Biol. 10: 51-58. Lappas, M., Yee, K., Permezel, M., and Rice, G.E. (2005) Sulfasalazine and BAY 11- 7082 interfere with the nuclear factor-kappa B and I kappa B kinase pathway to regulate the release of proinflammatory cytokines from human adipose tissue and skeletal muscle in vitro. Endocrinol. 146, 1491-1497 Larsen, T.M., Toubro, S., and Astrup, A. (2003) Efficacy and safety of dietary supplements containing CLA for the treatment of obesity: evidence from animal and human studies. J. Lipid Res. 44: 2234-2241 Lau, D.C., Dhillon, B., Yan, H., Szmitko, P.E., and Verma, S. (2005) Adipokines: molecular links between obesity and atherosclerosis. Am. J. <strong>Ph</strong>ysiol. Heart Circ. <strong>Ph</strong>ysiol. 288, H2031-2041 Lee, J.Y., Ye, J., Gao, Z., Youn, H.S., Lee, W.H., Zhao, L., Sizemore, N., and Hwang D.H. (2003) Reciprocal modulation of toll-like receptor-4 signaling pathways involving MyD88 and phosphatidylinositol 3-kinase/AKT <strong>by</strong> saturated and polyunsaturated fatty acids. J. Biol. Chem. 278: 37041-37051 Lee, K., Kritchevsky, D. and Pariza, M. (1994) <strong>Conjugated</strong> linoleic acid and atherosclerosis in rabbits. Atherosclerosis 108:19-25 Li, Z.W. (1999) The IKK beta subunit of IKK is essential for nuclear factor kappa B activation and prevention of apoptosis. J. Exp. Med. 189: 1839-1845 Li, X., Massa, P.E., Hanidu, A., Peet, G.W., Aro. P., Savitt, A., Mische, S., Li, J., and Marcu, K.B. (2002) IKKalpha, IKKbeta, and NEMO/IKKgamma are each required for the NF-kappa B-mediated inflammatory response program. J. Biol. Chem. 277, 45129- 45140 Lin, Y., Lee, H., Berg, A.H., Lisanti, M.P., Shapiro, L., and Scherer, P.E. (2000) The lipopolysaccharide-activated toll-like receptor (TRL)-4 induces synthesis of the closely related receptor TRL-2 in adipocytes. J. Biol. Chem. 278: 37041-37051 143
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CHUNG, SOONKYU, Ph. D. Mechanisms b
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MECHANISMS BY WHICH CONJUGATED LINO
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APPROVAL PAGE This Dissertation has
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I also would like to thank The Univ
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IV. PREADIPOCYTES MEDIATE LPS-INDUC
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LIST OF FIGURES ix Page Figure 1.1.
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Figure 4.7. LPS-induced NFκB activ
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in animals and some humans (reviewe
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CLA is potentially effective in: 1)
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Anti-adipogenic Mechanisms of CLA T
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2005). Chapter II of this dissertat
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Figure 1. 2. Multiple mechanisms by
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In contrast, studies conducted in a
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activation. Similarly, Chen et al.
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Central Hypothesis and Specific Obj
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CHAPTER II TRANS-10, CIS-12 CLA INC
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of MEK/ERK signaling by trans-10, c
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Materials and Methods Materials All
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the cultures for additional 12 h. A
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precipitated with ethanol, dried, a
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or for 30 min with 10 µM isoproter
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either 30 µM cis-9, trans-11 CLA o
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dependent effects of CLA on the pho
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Rapamycin Blocks CLA’s Increase i
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Figure 2. 2. Trans-10, cis-12 CLA a
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Figure 2. 4. Trans-10, cis-12 CLA a
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Figure 2. 6. Trans-10, cis-12 CLA i
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Figure 2. 8. Trans-10, cis-12 CLA-i
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Discussion Feeding mixed CLA isomer
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in lipolysis may occur via an ERK-d
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espectively, by the MEK inhibitor U
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Furthermore, the CLA-mediated incre
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proteins. Inhibition of NFκB activ
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Sopasakis et al. 2004) and insulin
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antibodies for anti-glyceraldehydre
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pM of human insulin in the presence
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were (accession #NM000600) sense (5
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Transfection efficiency was examine
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treatment (Brown et al. 2004), we d
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myotubes (Sinha et al. 2004; Weiger
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controls was found in cytosol (Fig
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Depletion of NFκB p65 by RNAi Atte
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eports of cytokine-mediated insulin
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Figure 3. 2. Trans-10, cis-12 CLA i
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Figure 3. 4. Trans-10, cis-12 CLA a
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Figure 3. 6. Trans-10, cis-12 CLA-i
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Figure 3. 8. Specific depletion of
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Figure 3. 10. Working model: Trans-
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Based on our working model (Fig 3.1
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mRNA levels of TNF-α (Fig. 3). How
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humans (Riserus et al. 2004a), and
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most likely not impairing the diffe
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