Ruan, H., Miles, P.D., Ladd, C.M., Ross, K., Golub, T.R,, Olefsky, J.M,, and Lodish, H.F. (2002) Profiling gene transcription in vivo reveals adipose tissue as an intermediate target for tumor necrosis alpha: implications for insulin resistance. Diabetes 51: 1376-3188 Ruan, H., Pownall, H., and Lodish H (2003) Troglitazone antagonizes tumor necrosis factor-a induced reprogramming of adipocyte gene expression <strong>by</strong> inhibiting the transcriptional regulatory functions of NFκB. J. Biol. Chem. 278: 28181-28192 Ryder, J.W., Portocarrero, C.P., Song, S.M., and Houseknecht K.L. (2001) Isomerspecific antidiabetic properties of conjugated linoleic acid. Improved glucose tolerance, skeletal muscle insulin action, and UCP-2 gene expression. Diabetes. 50:1149-1157. Saltiel, A.R. (2001) New perspective into the molecular pathogenesis and treatment of type 2 diabetes. Cell 104:517-529. Schmidt, C., Peng, B., Li, Z., Sclabas, G.M., Fujioka, S., Niu, J., Evans, D.B., Abbruzzese, J.L., and Chiao, P.J. (2003) Mechanism of proinflammatory cytokineinduced biphasic NFκB activation. Mol. Cell 12: 1287-1300. Sehat, N., Kramer, J.K., Mossoba, M.M., Yurawecz, M.P., Roach, J.A., Eulitz, K., Morehouse, K.M., and Ku, Y. (1998) Identification of conjugated linoleic acid isomers in cheese <strong>by</strong> gas chromatography, silver ion high performance liquid chromatography and mass spectral reconstructed ion profiles. Lipids 33:963-971. Serrero, G., Frolov, F., Schroeder, K., Tanaka, L., and Gelhaar, L. (2000) Adipose differentiation related protein: expression, purification of recombinant protein in Escherichia coli and characterization of its fatty acid binding properties. Biochem. Biophys. Acta. 1488: 245-254. Shao, D,, Rangwala, S.M,, Bailey, S.T., Krakow, S.L., Reginato, M.J, Lazar, M.A. (1998) Interdomain communication regulating ligand binding <strong>by</strong> PPAR-gamma. Nature 396:377-380 Shoelson, S.E., Lee, J., and Yuan, M. (2003) Inflammation and the IKKβ/IκB/NFκB axis in obesity- and diet-induced insulin resistance. Int. J. Obes. 27: 549-552 Shulman, G.I. (2000) Cellular mechanisms of insulin resistance. J. Clin. Invest. 106:171- 176 147
Sinha, S., Perdomo, G., Brown, N.F., and O’Doherty, R.M. (2004) Fatty acid-induced insulin resistance in L6 myotubes is prevented <strong>by</strong> inhibition of activation and nuclear localization of nuclear factor kappa B. J. Biol. Chem. 297:41294-41301 Skyler, J.S. and Oddo, C. (2002) Diabetes trends in the USA. Diabetes Metab. Res. Rev. 131:S21-26. Smedman, A., Basu, S., Jovinge, S., Fredrikson, G.N., and Vess<strong>by</strong>, B. (2005) <strong>Conjugated</strong> linoleic acid increased C-reactive protein in human subjects. Br. J. Nutr. 94:791-795. Soni, K., Lehner, R., Metalnikov, P., O'Donnell, P., Semache, M., Gao, W., Ashman, K., Pshezhetsky, A., and Mitchell, G. (2004) Carboxylesterase 3 (EC 3.1.1.1) is a major adipocyte lipase. J. Biol. Chem. 279: 40683- 40689 Sopasakis, V.R., Sandqvist, M., Gustafson, B., Hammarstedt, A., Schemelz, M., Yang, X., Jansson, P.A., and Smith, U. (2004) High local concentrations and effects on differentiation implicate interleukin-6 as a paracrine regulator. Obesity Res. 12, 454-460 Souza, S., de Vargas, L., Yamamoto, M., Lien, P., Franciosa, M., Moss, L., and Greenberg, A. (1998) Overexpression of perilipin A and B blocks the ability of tumor necrosis factor alpha to increase lipolysis in 3T3-L1 adipocytes. J. Biol. Chem. 273: 24665-24669. Spiegelman, B.M., and Flier, J.S. (2001) Obesity and the regulation of energy balance. Cell 104:531-541. Stuart, P.W., McCann, D., Desai, M., Rosenbaum, M., Leibel, R.L. (2003) Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest. 112:1796- 1808. Suzawa, M., Takada, I., Yanagisawa, J., Ohtake, F., Ogawa, S., Yamauchi, T., Kadowaki, T., Takeudhi, Y., Shibuya, H., Gotoh, Y., Matsumoto, K., and Kato, S. (2003) Cytokines suppress adipogenesis and PPARγ function through the TAK1/TAB1/NIK cascade. Nat. Cell Biol. 5: 224-230 Sztalryd, C., Xu, G., Dorward, H., Tansey, J., Contreras, J., Kimmel, A, and Landos, C. (2003) Perilipin A is essential for the translocation of hormone sensitive lipase during lipolytic activation. J. Cell Biol. 161: 1093-1103 148
- Page 1 and 2:
CHUNG, SOONKYU, Ph. D. Mechanisms b
- Page 3 and 4:
MECHANISMS BY WHICH CONJUGATED LINO
- Page 5 and 6:
APPROVAL PAGE This Dissertation has
- Page 7 and 8:
I also would like to thank The Univ
- Page 9 and 10:
IV. PREADIPOCYTES MEDIATE LPS-INDUC
- Page 11 and 12:
LIST OF FIGURES ix Page Figure 1.1.
- Page 13 and 14:
Figure 4.7. LPS-induced NFκB activ
- Page 15 and 16:
in animals and some humans (reviewe
- Page 17 and 18:
CLA is potentially effective in: 1)
- Page 19 and 20:
Anti-adipogenic Mechanisms of CLA T
- Page 21 and 22:
2005). Chapter II of this dissertat
- Page 23 and 24:
Figure 1. 2. Multiple mechanisms by
- Page 25 and 26:
In contrast, studies conducted in a
- Page 27 and 28:
activation. Similarly, Chen et al.
- Page 29 and 30:
Central Hypothesis and Specific Obj
- Page 31 and 32:
CHAPTER II TRANS-10, CIS-12 CLA INC
- Page 33 and 34:
of MEK/ERK signaling by trans-10, c
- Page 35 and 36:
Materials and Methods Materials All
- Page 37 and 38:
the cultures for additional 12 h. A
- Page 39 and 40:
precipitated with ethanol, dried, a
- Page 41 and 42:
or for 30 min with 10 µM isoproter
- Page 43 and 44:
either 30 µM cis-9, trans-11 CLA o
- Page 45 and 46:
dependent effects of CLA on the pho
- Page 47 and 48:
Rapamycin Blocks CLA’s Increase i
- Page 49 and 50:
Figure 2. 2. Trans-10, cis-12 CLA a
- Page 51 and 52:
Figure 2. 4. Trans-10, cis-12 CLA a
- Page 53 and 54:
Figure 2. 6. Trans-10, cis-12 CLA i
- Page 55 and 56:
Figure 2. 8. Trans-10, cis-12 CLA-i
- Page 57 and 58:
Discussion Feeding mixed CLA isomer
- Page 59 and 60:
in lipolysis may occur via an ERK-d
- Page 61 and 62:
espectively, by the MEK inhibitor U
- Page 63 and 64:
Furthermore, the CLA-mediated incre
- Page 65 and 66:
proteins. Inhibition of NFκB activ
- Page 67 and 68:
Sopasakis et al. 2004) and insulin
- Page 69 and 70:
antibodies for anti-glyceraldehydre
- Page 71 and 72:
pM of human insulin in the presence
- Page 73 and 74:
were (accession #NM000600) sense (5
- Page 75 and 76:
Transfection efficiency was examine
- Page 77 and 78:
treatment (Brown et al. 2004), we d
- Page 79 and 80:
myotubes (Sinha et al. 2004; Weiger
- Page 81 and 82:
controls was found in cytosol (Fig
- Page 83 and 84:
Depletion of NFκB p65 by RNAi Atte
- Page 85 and 86:
eports of cytokine-mediated insulin
- Page 87 and 88:
Figure 3. 2. Trans-10, cis-12 CLA i
- Page 89 and 90:
Figure 3. 4. Trans-10, cis-12 CLA a
- Page 91 and 92:
Figure 3. 6. Trans-10, cis-12 CLA-i
- Page 93 and 94:
Figure 3. 8. Specific depletion of
- Page 95 and 96:
Figure 3. 10. Working model: Trans-
- Page 97 and 98:
Based on our working model (Fig 3.1
- Page 99 and 100:
mRNA levels of TNF-α (Fig. 3). How
- Page 101 and 102:
humans (Riserus et al. 2004a), and
- Page 103 and 104:
most likely not impairing the diffe
- Page 105 and 106:
1) decreased adipogenic gene expres
- Page 107 and 108:
adipocytes from WAT in inflammation
- Page 109 and 110: differentiation, cultures of SV cel
- Page 111 and 112: Immunoblotting and 4MUrea-SDS-PAGE
- Page 113 and 114: activity was measured using the Dua
- Page 115 and 116: macrophages and myocytes, respectiv
- Page 117 and 118: cultures, insulin’s stimulation o
- Page 119 and 120: AD90 cultures treated with LPS. Con
- Page 121 and 122: Table 4.1. List of human-gene speci
- Page 123 and 124: Figure 4.2. Primary cultures of new
- Page 125 and 126: Figure 4.4 LPS induction of cytokin
- Page 127 and 128: Figure 4. 6. LPS suppresses PPARγ
- Page 129 and 130: Figure 4. 8. Inhibitors of NFκB at
- Page 131 and 132: Discussion Adipose tissue is a sour
- Page 133 and 134: To determine if non-adipocytes othe
- Page 135 and 136: attenuation of insulin sensitivity
- Page 137 and 138: epression of NFκB target gene expr
- Page 139 and 140: EPILOGUE The “Obesity epidemic’
- Page 141 and 142: Apart from our initial goal for thi
- Page 143 and 144: Concerning membrane specific recept
- Page 145 and 146: esearch topic I would like to exami
- Page 147 and 148: Berg, A.H., Lin, Y., Lisanti, M.P.,
- Page 149 and 150: Chen, C., Koh, A.J., Datta, N.S., Z
- Page 151 and 152: Diradourian, C., Girard, J., and Pe
- Page 153 and 154: Granlund, L., Juvet, L.K., Pedersen
- Page 155 and 156: Imamura, M., Inoguchi, T., Ikuyama,
- Page 157 and 158: Loscher, C.E., Draper, E., Leavy, O
- Page 159: Piper, R.C., Hess, L.J., and James,
- Page 163 and 164: Vanden Berghe, W., Vermeulen, L., D