Clifford, G., Londos, C., Kraemer, F., and Vernon, R. (2000) Translocation of hormonesensitive lipase and perilipin upon lipolytic stimulation of rat adipocytes. J. Biol. Chem. 275: 5011-15. Cohen, A., Razani, B., Schubert, W., Williams, T., Wang, X., Iyengar, P., Brasaemle D., Scherer. E., and Lisanti, M. (2004) Role of caveolin-1 in the modulation of lipolysis and lipid droplet formation. Diabetes 53: 1261-1270. Connolly, J.M., Gilhooly, E.M., and Rose, D.P. (1999) Effects of reduced dietary linoleic acid intake, alone or combined with an algal source of docosahexaenoicacid, on MDA- MB-231 breast cancer cell growth and apoptosis in nude mice. Nutr. Cancer 35:44–49. Cora, W., Brodbeck, K., Staiger, H., Kaush, C., Machicao, F., Häring, H.U. and Schleicher, E.D. (2004) Palmitate, but not unsatureated fatty acids, induces the expression of interleukin-6 in human myotubes through proteosome-dependent activation of nuclear factor-κB. J. Biol. Chem. 279: 23942-23952. Cousin, B., Munoz, O., and Andre, M. (1999) A role for preadipocytes as macrophagelike cells. FASEB J. 13:305-312. Covert, M.W., Leung, T.H., Gastpm, J.E., Baltimore, D. (2005) Achieving stability of lipopolisaccharide-induced NFκB activation. Science 309:1854-1857 Dalen, K., Schoonjans, K., Ulven, S., Weedon-Fekjaer, M., Bentzen, T., Koutnikova, A., Auwerx, J., and Nebb, H. (2004) Adipose tissue expression of lipid droplet-Association Proteins S3-12 and perilipin is controlled peroxisome proliferators activated receptor γ. Diabetes 53: 1243-1252. de Mora J., Porras, A., Ahn, N., and Santos, E. (1997) Mitogen-activated protein kinase activation is not necessary for, but antagonizes, 3T3-L1 adipocytic differentiation. Mol. Cell. Biol 17: 6068-6075 Delany, J., Blohm, F., Truett, A., Scimeca, J., and West, D. (1999) <strong>Conjugated</strong> linoleic acid rapidly reduces body fat content in mice without affecting energy intake. Am. J. <strong>Ph</strong>ysiol. 276: R1172-R1179. Desroches, S., Chouinard, P.Y., Galibois, I., Corneau, L., Delisle, J., Lamarche, B., Couture, P., and Bergeron, N. (2005) Lack of effect of dietary conjugated linoleic acids naturally incorporated into butter on the lipid profile and body composition of overweight and obese men. Am. J. Clin. Nutr. 82:309-319. Desvergne, B., and Wahli, W. (1999) Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocrinol. Rev. 20:649. 137
Diradourian, C., Girard, J., and Pegorier, J. (2005) <strong>Ph</strong>osphorylation of PPARs: from molecular characterization to physiological relevance. Biochemie 87:33-38 Dixit, V., and Mak, T.W. (2002) NF-kappaB signaling. Many roads lead to Madrid. Cell 111: 615-619 Ealey, K.N., El Sohemy, A., Archer, M.C. (2002) Effects of dietary conjugated linoleic acid on the expression of uncoupling proteins in mice and rats. Lipids 37:853-861. Evans, M., Geigerman, C., Cook, J., Curtis, L., Kuebler, B., and McIntosh, M. (2000) <strong>Conjugated</strong> linoleic acid suppresses triglyceride accumulation and induces apoptosis in 3T3-L1 preadipocytes. Lipids 35:899-910. Evans, M., Park, Y., Pariza, M., Curtis, L., Kuebler, B. and McIntosh M. (2001) Trans-10, cis-12 conjugated linoleic acid reduces triglyceride content while differentially affecting PPARγ2 expression in 3T3L1 preadipocytes. Lipids 36: 1223-1232 Evans, M., Brown, J.M. and McIntosh, M. (2002) Isomerspecific effects of conjugated linoleic acid on adiposity and lipid metabolism.J. Nutr. Biochem. 13:508-516 Fain, J.N., Madan, A.K., Hiler, M.L., Cheema, P., and Bahouth, S.W. (2004a) Comparison of the release of cytokines <strong>by</strong> adipose tissue, adipose tissue matrix, and adipocytes form visceral and subcutaneous abdominal adipose tissues of obese humans. Endocrinol. 145: 2273-2282 Fain, J.N., Bahouth, S.W., Madan, A.K. (2004b) TNF-α release <strong>by</strong> the nonfat cells of human adipose tissue. Int. J. Obesity 28: 616-623 Fang, H., Pengal, R.A, Cao, X., Ganesan, L.P., Wewers, M.D,, Marsh, C.B., and Tridandapani, S. (2004) Lipopolysaccharide-induced macrophage inflammatory response is regulated <strong>by</strong> SHIP. J. Immunol. 173: 360–366 Festa, A., D’Agostino, Jr. R., Williams, K., Karter, A.J., Mayer-Davis, E.J., Tracy, R.P., and Haffner, S.M. (2001) The relation of body fat mass and distribution to markers of chronic inflammation. Int. Obes. Relat. Metab. Disord. 25:1407-1415. Flegal, K.M., Carroll, M.D., Kuczmarski, R.J., Johnson, C.L. (1998) Overweight and obesity in the United States: prevalence and trends, 1960-1994. Int. J. Obes. Relat. Metab. Disord. 22:39-47. 138
- 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: Chen, C., Koh, A.J., Datta, N.S., Z
- 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 and 160: Piper, R.C., Hess, L.J., and James,
- Page 161 and 162: Sinha, S., Perdomo, G., Brown, N.F.
- Page 163 and 164: Vanden Berghe, W., Vermeulen, L., D