臺灣博碩士論文加值系統

肥胖已被認為是許多慢性疾病的危險因子，如高血壓、糖尿病及動脈粥狀硬化等。樟芝（Antrodia camphorata）之子實體已被證實具抗氧化、降血壓、抗癌、降血脂及保肝等功效，但樟芝對於體脂堆積的影響尚未被探討。因樟芝子實體中主要揮發性成分2,4,5-TMBA具有抑制COX-2活性，而COX-2在脂肪細胞分化中扮演了重要的角色，本實驗探討2,4,5-TMBA對於3T3-L1脂肪前驅細胞的分化及成熟脂肪細胞脂解能力之影響。以紅油染色方法顯示在分化階段，2,4,5-TMBA會隨著劑量的提升而抑制脂肪的形成。在分子層次上，2,4,5-TMBA會抑制參與細胞訊息傳遞路徑的MEK、ERK、JNK 及參與脂肪細胞中主要的轉錄因子 C/EBPs、PPAR γ、ADD1/SREBP1c 並抑制參與脂肪酸合成的acetyl-CoA carboxylase及脂肪細胞表面蛋白perilipin A的蛋白質表現量。當2,4,5-TMBA處理成熟脂肪細胞時，會提升荷爾蒙敏感性脂解酶HSL 及降低 perilipin A的蛋白質表現，而提升三酸甘油酯被水解的能力。綜合以上的結果顯示，2,4,5-TMBA會抑制3T3-L1脂肪前驅細胞的分化並促進成熟脂肪細胞內的脂質分解。

關鍵字： 2,4,5-TMBA、脂質合成、脂解能力、3T3-L1脂肪細胞

Obesity is considered a major risk factor for many chronic disease, including hypertension, type 2 diabetes, and atherosclerosis.The fruiting bodies of Antrodia camphorate possess various biological activites, including anti-oxidation, anti-hypertension, anti-carcinogenesis, anti-hyperlipidemia and liver-protection.
However, there has not been any study related to anti-obesity. The major volatile compound of Antrodia camphorate fruiting body, 2,4,5-trimethoxybenzaldehyde (2,4,5-TMBA), was reported to be a significantly inhibitor of COX-2 activity. Because COX-2 is essential for adipogenesis, we investigated the effect of 2,4,5-TMBA on 3T3-L1 preadipocytes differentiation and adipocytes lipolysis. During differentiation, 2,4,5-TMBA dose-dependently attenuated lipid accumulation in differentiated adipocyte as evidenced by Oil Red O staining. At the molecular level, 2,4,5-TMBA decreased the protein expression of MAP kinase kinsae (MEK), extracellular signal-regulated kinase (ERK), c-Jun amino-terminal kinase (JNK), CCAAT/enhancer binding protein (C/EBP) α,β,γ, peroxisome proliferator-activated receptor (PPAR) γ, adipocyte determination and differentiation-dependent factor1/sterol regulation element binding protein1c (ADD1/SREBP1c), acetyl-CoA carboxylase (ACC), and perilipin A. In mature adipocytes, 2,4,5-TMBA singnificantly decreased intracellular lipid accumulation by increasing the lipolysis of triglyceride though suppression of perilipin A and up-regulation of hormone-sensitive lipase (HSL). These results demonstrate that 2,4,5-TMBA efficiently inhibits adipogenesis and increase lipolysis in 3T3-L1 cells.

Keywords：2,4,5-TMBA, adipogenesis, lipolysis, 3T3-L1 cells

內容 頁次
審查通過證明書 I
博碩士論文電子檔案上傳授權書 II
致謝 III
目錄 IV
圖目錄 VI
表目錄 VII
摘要 VIII
Abstract XI
前言 1
壹、脂肪組織 2
貳、脂肪細胞之研究 5
一、脂肪前驅細胞之細胞株 5
二、脂肪前驅細胞分化過程 6
三、脂肪細胞脂質代謝 14
参、參與脂肪細胞分化及代謝相關基因之介紹 18
一、PPAR家族 18
二、CCAAT-增強子結合蛋白（C/EBPs） 20
三、環氧化酶（COX） 22
肆、樟芝 23
伍、實驗假說 28
材料與方法 29
一、實驗設計 29
二、樣品來源及配置 31
三、細胞之培養 31
四、誘導3T3-L1脂肪細胞分化 33
五、細胞毒性試驗（MTT assay） 36
六、測量脂質堆積情形 37
（一）油紅染色測定 37
（二）三酸甘油酯含量 40
七、脂肪細胞激素 41
（一）脂聯素 41
（二）瘦體素 42
八、成熟脂肪細胞lipolysis之測定（甘油釋放濃度） 43
九、原漿微粒蛋白質之分離 44
十、蛋白質定量 45
十一、電泳分析 45
十二、西方點墨法 47
十三、統計與分析 47
結果 53
一、2,4,5-TMBA對於脂肪前驅細胞分化之影響 53
（一）細胞毒殺性 53
（二）油紅染色測定 55
（三）三酸甘油酯含量測定 55
（四）MAPK蛋白質之表現 59
（五）脂肪細胞轉錄因子蛋白質之表現 62
（六）脂質合成相關蛋白質之表現 66
二、2,4,5-TMBA對於成熟脂肪細胞之影響 69
（一）油紅染色測定 69
（二）三酸甘油酯含量測定 69
（三）成熟脂肪細胞釋放甘油之含量 75
（四）成熟脂肪細胞分泌脂肪激素 75
（五）脂肪分解相關蛋白質之表現 79
（六）脂肪激素蛋白質之表現 80
討論 82
結論 94
文獻回顧 96

Albrektsen, T. Frederiksen, K.-S., Holmes, W.-E., Boel, E., Taylor, K., Fleckner, J.(2002), Novel genes regulated by the insulin sensitizer rosiglitazone during adipocyte differentiation. Diabetes, 51:1042-1051.

Ao, Z.-H., Xu, Z.-H., Lu, Z.-M., Xu, H.-Y., Zhang, X.-M., Dou, W.-F. (2009). Niuchangchih (Antrodia camphorata) and its potential in treating liver diseases. Journal of Ethnopharmacology, 121:194-212.

Bernlohr, D., Bolanowski, M., Kelly, T., Lane ,M.-D. (1985). Evidence for an increase in transcription of specific mRNAs during differentiation of 3T3-L1 preadipocytes. Journal of Biological Chemistry, 260:5563-5567.

Bishop-Bailey, D., Hla, T. (1999). Endothelial cell apoptosis induced by the peroxisome proliferator-activated receptor (PPAR) ligand 15-deoxy-Δ12, 14-prostaglandin J2. Journal of Biological Chemistry, 274:17042-17048.

Bishop‐Bailey, D. (2000). Peroxisome proliferator‐activated receptors in
the cardiovascular system. British journal of pharmacology, 129:823-834.

Bost, F., Aouadi. M., Caron, L., Binétruy, B. (2005a). The role of MAPKs in adipocyte differentiation and obesity. Biochimie, 87:51-56.

Bost, F., Aouadi, M., Caron, L., Even, P., Belmonte, N., Prot, M., Dani, C., Hofman, P., Pagès, G., Pouysségur, J. (2005b). The extracellular signal–regulated kinase isoform ERK1 is specifically required for in vitro and in vivo adipogenesis. Diabetes, 54:402-411.

Bernlohr, D., Bolanowski, M., Kelly, T., Lane, M.-D. (1985). Evidence for an increase in transcription of specific mRNAs during differentiation of 3T3-L1 preadipocytes. Journal of Biological Chemistry, 260:5563-5567.

Bishop-Bailey, D., Hla, T. (1999). Endothelial cell apoptosis induced by the peroxisome proliferator-activated receptor (PPAR) ligand 15-deoxy-Δ12, 14-prostaglandin J2. The Journal of Biological Chemistry, 274:17042-17048.

Brasaemle, D.-L. (2007). Thematic review series: adipocyte biology. The perilipin family of structural lipid droplet proteins: stabilization of lipid droplets and control of lipolysis. Journal of Lipid Research, 48:2547-2559.

Brasaemle, D.-L., Rubin, B., Harten, I.-A., Gruia-Gray, J., Kimmel, A.-R., Londos, C. (2000). Perilipin A increases triacylglycerol storage by decreasing the rate of triacylglycerol hydrolysis. The Journal of Biological Chemistry, 275:38486-38493.

Cannon, B., Nedergaard, J. (2004). Brown adipose tissue: function and physiological significance. Physiological Reviews, 84:277-359.

Cao, Z., Umek, R., McKnight, S. (1991). Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells. Genes & Development, 5:1538-1552.

Chen, C.-C., Chyau, C.-C., Hseu, T.-H. (2007). Production of a COX-2 inhibitor, 2,4,5-trimethoxy benzaldehyde, with submerged cultured Antrodia camphorata. Letters in Applied Microbiology, 44:387-392.

Chen, C.-H., Yang, S.-W., Shen, Y.-C. (1995). New steroid acids from Antrodia cinnamomea, a fungal parasite of Cinnamomum micranthum. Journal of Natural Products, 58:1655-1661.

Chen, H.-C., Farese, R.-V. (2002). Determination of adipocyte size by computer image analysis. Journal of Lipid Research, 43:986-989.

Cornelius, P., MacDougald, O.-A., Lane, M.-D. (1994). Regulation of adipocyte development. Annual Review of Nutrition, 14:99-129.

Cornelius, P., Enerback ,S., Bjursell, G., Olivecrona, T., Pekala, P.-H. (1988). Regulation of lipoprotein lipase mRNA content in 3T3-L1 cells by tumour necrosis factor. Biochemical Journal, 249:765-769.

Cowherd, R.-M., Lyle, R.-E., McGehee, Jr.-R.-E. (1999). Molecular regulation of adipocyte differentiation. Cell & Development Biology, 10:3-10.

Dani, C., Amri, E.-Z., Bertrand, B., Enerback, S., Bjursell, G., Grimaldi, P., Ailhaud, G. (1990). Expression and regulation of pOb24 and lipoprotein lipase genes during adipose conversion. Journal of Cellular Biochemistry, 43:103-110.

Darlington, G.-J., Ross, S.-E., MacDougald, O.-A. (1998). The role of C/EBP genes in adipocyte differentiation. The Journal of Biological Chemistry, 273:30057-30060.

Dowell, P., Flexner, C., Kwiterovich, P.-O., Lane, M.-D. (2000). Suppression of preadipocyte differentiation and promotion of adipocyte death by HIV protease inhibitors. The Journal of Biological Chemistry, 275:41325-41332.

El-Jack, A.-K., Hamm, J.-K., Pilch, P.-F., Farmer, S.-R. (1999). Reconstitution of insulin-sensitive glucose transport in fibroblasts requires expression of both PPARγ and C/EBPα. The Journal of Biological Chemistry, 274:7946-7951.

Fajas, L., Miard, S., Briggs, M.-R., Auwerx, J. (2003). Selective cyclo-oxygenase-2 inhibitors impair adipocyte differentiation through inhibition of the clonal expansion phase. Journal of Lipid Research, 44:1652-1659.

Fasshauer, M., Klein, J., Neumann, S., Eszlinger, M., Paschke, R. (2002).
Hormonal regulation of adiponectin gene expression in 3T3-L1 adipocytes. Biochemical and Biophysical Research Communications, 290:1084-1089.

Friedman, J.-M., Halaas, J.-L. (1998). Leptin and the regulation of body weight in mammals. Nature, 395:763-770.


Fu, Y., Luo, N., Klein, R.-L., Garvey, W.-T. (2005). Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation. Journal of lipid research, 46:1369-1379.

Ghoshal, S., Trivedi D, B., Graf, G.-A., Loftin, C.-D. (2011) Cyclooxygenase-2 deficiency attenuates adipose tissue differentiation and inflammation in mice. Journal of Biological Chemistry, 286:889-898.

Gaidhu, M.-P., Fediuc, S., Anthony, N.-M., So, M., Mirpourian, M., Perry, R.-L.-S., Ceddia, R.B. (2009). Prolonged AICAR-induced AMP-kinase activation promotes energy dissipation in white adipocytes: novel mechanisms integrating HSL and ATGL. Journal of Lipid Research, 50:704-715.

Garcia de Herreros, A., Birnbaum, M. (1989). The regulation by insulin of glucose transporter gene expression in 3T3 adipocytes. The Journal of Biological Chemistry, 264:9885-98890.

Green, H., Meuth, M. (1974). An established pre-adipose cell line and its differentiation in culture. Cell, 3:127-133.

Gregoire, F.-M., Smas, C.-M., Sul, H.-S. (1998). Understanding adipocyte differentiation. Physiological Reviews, 78:783-809.

Harmon, A.-W., Paul, D-.S., Patel, Y.-M. (2004). MEK inhibitors impair insulin-stimulated glucose uptake in 3T3-L1 adipocytes. American Journal of Physiology-Endocrinology and Metabolism, 287:E758-E766.

Hata, K., Nishimura, R., Ikeda, F., Yamashita, K., Matsubara, T., Nokubi, T., Yoneda, T. (2003). Differential roles of Smad1 and p38 kinase in regulation of peroxisome proliferator-activating receptor γ during bone morphogenetic protein 2-induced adipogenesis. Molecular Biology of The Cell, 14:545-555.

Hauner, H. (2004). The new concept of adipose tissue function. Physiology & Behavior, 83:653-658.

Hollenberg, A.-N., Susulic, V.-S., Madura, J.-P., Zhang, B., Moller, D.-E., Tontonoz, P., Sarraf, P., Spiegelman, B.-M., Lowell, B.-B. (1997). Functional antagonism between CCAAT/enhancer binding protein-α and peroxisome proliferator-activated receptor-γ on the leptin promoter. The Journal of Biological Chemistry, 272:5283-5290.

Houseknecht, K.-L., Cole, B.-M., Steele, P.-J. (2002). Peroxisome proliferator-activated receptor gamma (PPARγ) and its ligands: a review. Domestic Animal Endocrinology, 22:1-23.

Hseu, Y.-C., Yang, H.-L., Lai, Y.-C., Lin, J.-G., Chen, G.-W., Chang, Y.-H. (2004). Induction of apoptosis by Antrodia camphorata in human premyelocytic leukemia HL-60 cells. Nutrition and Cancer, 48:189-197.

Hseu, Y.-C., Chang, W.-C., Hseu, Y.-T., Lee, C.-Y., Yech, Y.-J., Chen, P.-C., Chen, J.-Y., Yang, H.-L. (2002). Protection of oxidative damage by aqueous extract from Antrodia camphorata mycelia in normal human erythrocytes. Life Sciences, 71:469-482.

Hsu, C.-L., Yen, G.-C. (2007). Effects of capsaicin on induction of apoptosis and inhibition of adipogenesis in 3T3-L1 cells. Journal of Agricultural and Food Chemistry, 55:1730-1736.

Huypens, P., Quartier, E., Pipeleers, D., Van de Casteele, M. (2005). Metformin reduces adiponectin protein expression and release in 3T3-L1 adipocytes involving activation of AMP activated protein kinase. European Journal of Pharmacology, 518:90-95.

Hwang, J.-T., Park, I.-J., Shin, J.-I., Lee, Y.-K., Lee, S.-K., Baik, H.-W., Ha, J., Park, O.-J. (2005). Genistein, EGCG, and capsaicin inhibit adipocyte differentiation process via activating AMP-activated protein kinase. Biochemical and Biophysical Research Communications, 338:694-699.

Kang, S.-I., Jin, Y.-J., Ko, H.-C., Choi, S.-Y., Hwang, J.-H., Whang, I., Kim, M.-H., Shin, H.-S., Jeong, H.-B., Kim, S.-J. (2008). Petalonia improves glucose homeostasis in streptozotocin-induced diabetic mice. Biochemical and Biophysical Research Communications, 373:265-269.

Kang, S.-I., Kim, M.-H., Shin, H.-S., Kim, H.-M., Hong, Y.-S., Park, J.-G., Ko, H.-C., Lee, N.-H., Chung, W.-S., Kim, S.-J. (2010). A water-soluble extract of Petalonia binghamiae inhibits the expression of adipogenic regulators in 3T3-L1 preadipocytes and reduces adiposity and weight gain in rats fed a high-fat diet. The Journal of Nutritional Biochemistry, 21:1251-1257.

Kern, P.-A., Ranganathan, S., Li, C., Wood, L., Ranganathan, G. (2001). Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. American Journal of Physiology-Endocrinology and Metabolism, 280:E745-E751.

Kershaw, E.-E., Flier, J.-S. (2004). Adipose tissue as an endocrine organ. Journal of Clinical Endocrinology & Metabolism, 89:2548-2556.

Kroemer, G., Petit, P., Zamzami, N., Vayssiere, J., Mignotte, B. (1995). The biochemistry of programmed cell death. The FASEB Journal, 9:1277-1287.

Kong, C.-S., Kim, J., Eom, T.-K., Kim, S.-K. (2010). Phosphorylated glucosamine inhibits adipogenesis in 3T3-L1 adipocytes. The Journal of Nutritional Biochemistry, 21:438-443.

MacDougald, O.-A., Hwang, C.-S., Fan, H., Lane, M.-D. (1995). Regulated expression of the obese gene product (leptin) in white adipose tissue and 3T3-L1 adipocytes. Proceedings of the National Academy of Sciences, 92:9034-9037.

Maeda, N., Takahashi, M., Funahashi, T., Kihara, S., Nishizawa, H., Kishida, K., Nagaretani, H., Matsuda, M., Komuro, R., Ouchi, N. (2001). PPARγ ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes, 50:2094-2099.

Mandrup, S., Lane, M.-D. (1997). Regulating adipogenesis. The Journal of Biological Chemistry, 272:5367-5370.

Mantzoros, C.-S. (1999). The role of leptin in human obesity and disease: a review of current evidence. Annals of Internal Medicine, 130:671-680.

Mayr, B.-M., Canettieri, G., Montminy, M.-R. (2001). Distinct effects of cAMP and mitogenic signals on CREB-binding protein recruitment impart specificity to target gene activation via CREB. Proceedings of the National Academy of Sciences, 98:10936-10941.

Mitchell, J.-A., Larkin, S., Williams, T.-J. (1995). Cyclooxygenase-2: regulation and relevance in inflammation. Biochemical Pharmacology 50:1535-1542.

Moller, D.-E. (2000). Potential role of TNF-[alpha] in the pathogenesis of insulin resistance and type 2 diabetes. Trends in Endocrinology and Metabolism, 11:212-217.

Momin, R.-A., De Witt, D.-L., Nair, M.-G. (2003). Inhibition of cyclooxygenase (COX) enzymes by compounds from Daucus carota L. seeds. Phytotherapy Research, 17:976-979.

Newton, B.-W., Cologna, S.-M., Moya, C., Russell, D.-H., Russell, W.-K., Jayaraman, A. (2011). Proteomic analysis of 3T3-L1 adipocyte mitochondria during differentiation and enlargement. Journal of Proteome Research, 10:4692-4702.

Ntambi, J.-M., Young-Cheul, K. (2000). Adipocyte differentiation and gene expression. The Journal of Nutrition, 130:3122S-3126S.

Otto, T.-C., Lane, M.-D. (2005). Adipose development: from stem cell to adipocyte. Critical Reviews in Biochemistry and Molecular Biology, 40:229-242.

Prins, J.-B., Walker, N.-I., Winterford, C.-M., Cameron, D.-P. (1994). Human adipocyte apoptosis occurs in malignancy. Biochemical and Biophysical Research Communications, 205:625-630.

Prusty, D., Park, B.-H., Davis, K.-E., Farmer, S.-R. (2002a). Activation of MEK/ERK signaling promotes adipogenesis by enhancing peroxisome
proliferator-activated receptor γand C/EBPα gene expression during the differentiation of 3T3-L1 preadipocytes. The Journal of Biological Chemistry, 277:46226-46232.

Prusty, D., Park, B.-H., Davis, K.-E., Farmer, S.-R. (2002b). Activation of MEK/ERK signaling promotes adipogenesis by enhancing peroxisome proliferator-activated receptor γ (PPARγ) and C/EBPα gene expression during the differentiation of 3T3-L1 preadipocytes. Journal of Biological Chemistry, 277:46226-46232.

Reichert, M., Eick, D. (1999). Analysis of cell cycle arrest in adipocyte differentiation. Oncogene, 18:459-466.

Reshef, L., Olswang, Y., Cassuto, H., Blum, B., Croniger, C.-M., Kalhan, S.-C., Tilghman, S.-M., Hanson, R.-W. (2003). Glyceroneogenesis and the triglyceride/fatty acid cycle. The Journal of Biological Chemistry, 278:30413-30416.

Reznikoff, C.-A., Brankow, D.-W., Heidelberger, C. (1973). Establishment and characterization of a cloned line of C3H mouse embryo cells sensitive to postconfluence inhibition of division. Cancer Research, 33:3231-3238.

Ricquier, D., Bouillaud, F. (2000). Mitochondrial uncoupling proteins: from mitochondria to the regulation of energy balance. The Journal of Physiology 529:3-10.

Roncari, D.-A.-K., Lau, D.-C.-W., Kindler, S. (1981). Exaggerated replication in culture of adipocyte precursors from massively obese persons. Metabolism, 30:425-427.

Rosen, E.-D., Walkey, C.-J., Puigserver, P., Spiegelman, B.-M. (2000). Transcriptional regulation of adipogenesis. Genes & Development 14:1293-1307.

Russell, T.-R., Ho, R. (1976). Conversion of 3T3 fibroblasts into adipose cells: triggering of differentiation by prostaglandin F2alpha and 1-methyl-3-isobutyl xanthine. Proceedings of the National Academy of Sciences, 73:4516-4520.

Sale, E., Atkinson, P., Sale, G. (1995). Requirement of MAP kinase for differentiation of fibroblasts to adipocytes, for insulin activation of p90 S6 kinase and for insulin or serum stimulation of DNA synthesis. The EMBO Journal, 14:674-.684

Scherer, P.-E., Williams, S., Fogliano, M., Baldini, G., Lodish, H.-F. (1995). A novel serum protein similar to C1q, produced exclusively in adipocytes. The Journal of Biological Chemistry, 270:26746-26749.

Sheng, G., Shao, J., Sheng, H., Hooton, E., Isakson, P., Morrow, J., Coffey, R., DuBois, R., Beauchamp, R. (1997). A selective cyclooxygenase 2 inhibitor suppresses the growth of H-ras-transformed rat intestinal epithelial cells. Gastroenterology, 113:1883-1891.

Spiegelman, B.-M., Flier, J.-S. (1996). Adipogenesis and obesity: rounding out the big picture. Cell, 87:377-389.

Steinbach, G., Lynch, P.-M., Phillips, R.-K.-S., Wallace, M.-H., Hawk, E., Gordon, G.-B., Wakabayashi, N., Saunders, B., Shen, Y., Fujimura, T. (2000) .The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. New England Journal of Medicine, 342:1946-1952.

Steinberg, D., Vaughan, M., Margolis, S. (1961). Studies of triglyceride biosynthesis in homogenates of adipose tissue. The Journal of Biological Chemistry, 236:1631-1637.

Student, A., Hsu, R., Lane, M. (1980). Induction of fatty acid synthetase synthesis in differentiating 3T3-L1 preadipocytes. The Journal of Biological Chemistry, 255:4745-4570.

Tamori,Y., Masugi, J., Nishino, N., Kasuga, M. (2002). Role of peroxisome proliferator-activated receptor-γ in maintenance of the characteristics of mature 3T3-L1 adipocytes. Diabetes, 51:2045-2055.

Tanaka, T., Yoshida, N., Kishimoto, T., Akira, S. (1997). Defective adipocyte differentiation in mice lacking the C/EBPβ and/or C/EBPδ gene. The EMBO Journal, 16:7432-7443.

Tang, Q.-Q., Zhang, J.-W., Daniel Lane, M. (2004). Sequential gene promoter interactions of C/EBP [beta], C/EBP [alpha], and PPAR [gamma] during adipogenesis. Biochemical and Biophysical Research Communications, 319:235-239.

Taylor, S.-M., Jones, P.-A. (1979). Multiple new phenotypes induced in and 3T3 cells treated with 5-azacytidine. Cell, 17:771-779.

Tontonoz, P., Spiegelman, B.-M. (2008). Fat and beyond: the diverse biology of PPARγ. Annual Review of Biochemistry, 77:289-312.

Tontonoz, P., Kim, J., Graves, R., Spiegelman, B. (1993). ADD1: a novel helix-loop-helix transcription factor associated with adipocyte determination and differentiation. Molecular and Cellular Biology, 13:4753-4759.


Vázquez-Vela, M.-E.-F., Torres, N., Tovar, A.-R. (2008). White adipose tissue as endocrine organ and its role in obesity. Archives of Medical Research, 39:715-728.

Weyer, C., Funahashi, T., Tanaka, S., Hotta, K., Matsuzawa, Y., Pratley, R.-E., Tataranni, P.-A. (2001). Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. Journal of Clinical Endocrinology & Metabolism, 86:1930-1935.

Wu, S.-H., Ryvarden, L. (1997). Antrodia camphorata (" niu-chang-chih"), new combination of a medicinal fungus in Taiwan. Botanical Bullrtin of Academia Sinica, 38:273-276.

Wu, Z., Xie, Y., Bucher, N., Farmer, S.-R. (1995). Conditional ectopic expression of C/EBP beta in NIH-3T3 cells induces PPAR gamma and stimulates adipogenesis. Genes & Development, 9:2350-2363.

Yan, H., Kermouni, A., Abdel-Hafez, M., Lau, D.-C.-W. (2003). Role of cyclooxygenases COX-1 and COX-2 in modulating adipogenesis in 3T3-L1 cells. Journal of Lipid Research, 44:424-429.

Yang, J.-Y., Della-Fera, M.-A., Hartzell, D.-L., Nelson-Dooley, C., Hausman, D.-B., Baile, C.-A. (2006). Esculetin induces apoptosis and inhibits adipogenesis in 3T3-L1 cells. Obesity, 14:1691-1699.

Yun, J.-W. (2010). Possible anti-obesity therapeutics from nature-A review. Phytochemistry, 71:1625-1641.