臺灣博碩士論文加值系統

4-Hydroxynonenal(4-HNE)是一種脂質過氧化物，當體內有過多的自由基時，
自由基會去攻擊細胞膜上的多元不飽和脂肪酸，使脂質過氧化物增加，過去的研
究指出，在肥胖及第二型糖尿病人的血液中都有較高濃度的4-HNE，也有研究
發現，4-HNE 會促進脂肪細胞的脂解作用，並且增加游離脂肪酸的釋出，而過
多的游離脂肪酸會去抑制insulin/phosphoinositide 3-kinase(PI3K)/ protein kinase B (Akt)路徑，進而產生胰島素阻抗，且4-HNE 也會透過增加acetyl-CoA carboxylase(ACC)的蛋白質表現與malonyl-CoA 的濃度，進而去抑制脂肪酸β氧化，此外也發現，研究指出phase II 解毒榖胱甘肽硫轉移酶(glutathione S-transferases, GSTs)能代謝體內的4-HNE，進而降低 4-HNE 共軛蛋白對細胞造成的毒性。鼠尾草酸(carnosic acid, CA)是迷迭香中的多酚類，具有抗氧化、抗發炎及降血脂的功效，在本實驗室先前的研究中發現，CA 可以抑制TNF-α 誘發的發炎反應及胰島素阻抗，但是CA 對於4-HNE 誘發脂解作用及抑制脂肪酸β氧化的機制目前尚未明確，因此本研究利用分化成熟的 3T3-L1 脂肪細胞為模式，探討CA 對於4-HNE促進脂肪細胞脂解作用與抑制脂肪酸β氧化的影響。首先，成熟的3T3-L1脂肪細胞給予10-40 μM 的4-HNE，發現 4-HNE 能夠增加游離脂肪酸的釋出及磷酸化脂解酶hormone sensitive ipase (HSL)及其上游protein kinase A (PKA)的蛋白質表現；然而，預處理 CA 則能夠降低4-HNE 所活化的PKA及HSL之蛋白質表現，此外，CA 也能夠回復4-HNE 對磷酸化 AMP-activated protein kinase(AMPK)及磷酸化 ACC 的抑制(p<0.05)，當以5 μM 的AMPK 抑制劑compound C 和 CA 共處理24 小時再處理4-HNE 2小時後發現，compound C 能夠明顯地抑制CA 所回復的磷酸化 AMPK 及磷酸化 ACC 的蛋白質表現(p<0.05)。另外，我們也發現細胞處理4-HNE 在3和5小時會有較高的4-HNE共軛蛋白產生，若預處理CA 24小時則能明顯地減少4-HNE共軛蛋白的產生(p<0.05)。同時也發現，CA 能隨時間增加 GSTs 的蛋白質表現及酵素活性，當細胞預處理 5 μM 的 GSTs 抑制劑 ethacrynic
acid (EA)1 小時後，則會破壞CA 減少 4-HNE 共軛蛋白的能力。由以上結果發
現，CA 可能藉由活化抗氧化酵素 GSTs 來降低 4-HNE 共軛蛋白的產生，進而減
少 4-HNE 對3T3-L1脂肪細胞的脂解作用，並促進細胞的脂肪酸β氧化，最後減
少游離脂肪酸產生的胰島素阻抗。

4-Hydroxynonenal (4-HNE) is one of the lipid peroxidation products. When it has much free radical in cells, free radical will attack polyunsaturated lipid in cell membrane, and then lead to lipid peroxidation. Study indicated that the patients of obesity and type 2 diabetes mellitus had higher concentration of 4-HNE in the blood. Moreover, 4-HNE increases lipolysis and enhances free fatty acid release in
adipocytes. High concentration of free fatty acids inhibits insulin/PI3K/Akt pathway, and causes insulin resistance. Besides, 4-HNE inhibited β-oxidation via increasing the
protein expression of acetyl-CoA carboxylase (ACC) and malonyl-CoA content. Moreover, glutathione S-transferases (GSTs) can conjugate 4-HNE to non-toxic products and then decrease the toxicity by 4-HNE in cells. Carnosic acid (CA) is a rosemary (Rosmarinus officinalis)diterpene compound, possess multiple biological functions, such as anti-oxidant, anti-inflammatory and anti-adipogenic activities. But the mechanisms of CA on 4-HNE-induced lipolysis and 4-HNE-inhibited β-oxidation are still unknown. The purpose of this study is to investigate the mechanisms of CA on 4-HNE-induced lipolysis and 4-HNE-inhibited β-oxidation in 3T3-L1 adipocytes. The results shows that cells treated with 10-40 μM 4-HNE increased the release of free fatty acid in a dose-dependent manner. Pretreatment with CA inhibited the free
fatty acid released by 4-HNE (p<0.05).Cells treated with 10 to 40 μM of 4-HNE with or without pretreatment with CA had no cell damage in 3T3-L1 adipocytes. CA inhibited 4-HNE-induced the phosphorylation of protein kinase A (PKA) and
hormone sensitive lipase (HSL), and increased 4-HNE-suppressed the phosphorylation of AMP-activated protein kinase (AMPK) and ACC. 3T3-L1 adipocytes pretreated with compound C (AMPK inhibitor) decreased the phosphorylation of AMPK and ACC by CA (p<0.05).Cells treated with 4-HNE for 3
and 5 h increased the 4-HNE-conjugated proteins. Moreover, CA increased the protein expression and enzyme activity of GSTs. 3T3-L1 adipocytes treated with 5 μM of
ethacrynic acid, a GSTs inhibitor, blocked the CA decreased the 4-HNE-conjugated proteins (p<0.05). In conclusion, CA inhibited the lipolytic response and promote the β-oxidation by 4-HNE is likely related to the induction of GSTs via PKA/HSL and AMPK/ACC pathway.

目錄...................................... ii
圖次....................................... v
表次...................................... vi
縮寫表.................................... vii
中文摘要................................... 1
Abstract ................................. 3
第一章 前言................................ 5
第二章 文獻回顧............................. 6
一、 肥胖 .................................. 6
(一) 脂肪細胞的特性 ..................... 6
(二) 3T3-L1 前脂肪細胞的分化 ............. 8
二、 肥胖造成的氧化壓力與脂解作用 ............... 9
三、 脂肪細胞的脂解作用 ....................... 10
(一) Perilipin (PLIN) ..................... 11
(二) Adipocyte triglyceride lipase (ATGL).. 12
(三) Hormone sensitive lipase (HSL) ....... 13
(四)其他促脂解因子............................ 15
四、胰島素訊息傳遞路徑 (Insulin signaling pathway) ... 16
五、游離脂肪酸與胰島素阻抗 ..................... 17
六、脂肪酸的合成 ............................. 18
七、脂肪酸 β 氧化 ............................ 19
八、4-hydroxy-2-nonenal (4-HNE) ............ 20
(一) 4-HNE 與肥胖 ....................... 20
(二) 4-HNE 與神經退化性疾病的關係 .......... 21
(三) 4-HNE 對脂肪細胞脂解作用的影響 ........ 22
(四) 4-HNE 對脂質 β 氧化的影響 ............ 22
(五) 4-HNE 對脂肪細胞胰島素敏感性的的影響 .... 23
(六) 4-HNE 的代謝 ....................... 24
九、榖胱甘肽硫轉移酶(Glutathione S-transferases, GSTs)..... 25
十、迷迭香酸 (Carnosic acid, CA) ............. 26
(一)抗氧化 .............................. 26
(二)抗發炎 .............................. 27
(三)抑制脂質新生 ......................... 27
第三章 研究動機.............................. 28
第四章 材料與方法............................. 29
第五章 實驗結果............................... 44
一、CA 對 4-HNE 誘發 3T3-L1 脂肪細胞游離脂肪酸釋出及細胞存活率之影響
.................................................... 44
二、CA 降低 4-HNE 誘發的脂解酶 HSL 及其上游 PKA 之蛋白質表現 ....................................................... 44
三、CA 回復 4-HNE 降低 AMPK 及 ACC 磷酸化 ....................................................... 45
四、CA 透過增加 AMPK/ACC 路徑而增加脂肪酸 β 氧化 ....................................................... 46
五、CA 降低 4-HNE 在脂肪細胞內產生的共軛結合蛋白 ....................................................... 46
六、CA 透過增加 GSTs 的蛋白質表現與酵素活性而減少 4-HNE 誘發共軛蛋白
的產生 ............................................... 47
第六章 討論............................................. 55
第七章 結論............................................. 60
第八章 參考文獻......................................... 61

侯敏、馬秀敏與丁劍冰，2009，唇形科植物抗炎、抗過敏和抗氧化活性研究進展。
科技導報。27, 98-101。
Bezaire V., Mairal A., Anesia R., Lefort C. and Langin D., 2009. Chronic TNFα and cAMP pre-treatment of human dipocytes alter HSL,ATGL and perilipin to regulate basal and timulated lipolysis. FEBS Letters 583, 3045-3049.
Baile C. A., Yang J.-Y., Rayalam S., Hartzell D. L., Lai C.-Y., Andersen C. and Della-Fera M. A., 2011. Effect of resveratrol on fat mobilization. Annals of the New York
Academy of Sciences 1215, 40-47.
Beller M., Bulankina A. V., Hsiao H.-H., Urlaub H., ckle H. J. and hnlein R. P. K., 2010. Perilipin-dependent control of lipid droplet structure and fat storage in Drosophila.Cell Metabolism 12, 521-532.
Bezaire V., Mairal A., Ribet C., Lefort C., Girousse A., Jocken J., Laurencikiene J., Anesia R., Rodriguez A. M., Ryden M., Stenson B. M., Dani C., Ailhaud G., Arner P. and Langin D., 2009. Contribution of adipose triglyceride lipase and hormone-sensitive lipase to lipolysis in hMADS adipocytes. The Journal of Biological Chemistry 284, 18282-91.
Bickel P. E., Tansey J. T. and Welte M. A., 2009. PAT proteins, an ancient family of lipid droplet proteins that regulate cellular lipid stores. Biochimica et Biophysica Acta 1791, 419-40.
Bijland S., Mancini S. J. and Salt I. P., 2013. Role of AMP-activated protein kinase in adipose tissue metabolism and inflammation. Clinical Science 124, 491-507.
Boden G., 2011. Obesity, insulin resistance and free fatty acids. Current Opinion in Endocrinology, Diabetes & Obesity 18, 139-143.
Brownlee M., 2001. Biochemistry and molecular cell biology of diabetic complications. Nature 414, 813-20.
Capurso C. and Capurso A., 2012. From excess adiposity to insulin resistance: The role of free fatty acids. Vascular Pharmacology 57, 91-97.
Chapple S. J., Cheng X. and Mann G. E., 2013. Effects of 4-hydroxynonenal on vascular endothelial and smooth muscle cell redox signaling and function in health and disease. Redox biology 1, 319-31.
Chaves V. E., Frasson D. and Kawashita N. H., 2011. Several agents and pathways regulate lipolysis in adipocytes. Biochimie 93, 1631-1640.
Cohen G., Riahi Y., Sunda V., Deplano S., Chatgilialoglu C., Ferreri C., Kaiser N. and Sasson S., 2011. Signaling properties of 4-hydroxyalkenals formed by lipid peroxidation in diabetes. Free Radical Biology and Medicine 65, 978-987.
Coppack S. W., Jensen M. D. and Miles J. M., 1994. In vivo regulation of lipolysis in humans. Journal of Lipid Research 35, 177-193.
Dasuri K., Ebenezer P., Fernandez-Kim S. O., Zhang L., Gao Z., Bruce-Keller A. J., Freeman L. R. and Keller J. r. N., 2013. Role of physiological levels of 4-hydroxynonenal on adipocyte biology: implications for obesity and metabolic
syndrome. Free Radical Research 47, 8-19.
Demozay D., Mas J.-C., Rocchi S. and Obberghen E. V., 2008. FALDH reverses the deleterious action of oxidative stress induced by lipid peroxidation product 4-hydroxynonenal on insulin signaling in 3T3-L1 adipocytes. Diabetes 57,
1216-1226.
Folmes C. D. L. and Lopaschuk G. D., 2007. Role of malonyl-CoA in heart disease and the hypothalamic control of obesity. Cardiovascular Research 73, 278-287.
Friguet B., Szweda L. I. and Stadtman E. R., 1994. Susceptibility of glucose-6-phosphate dehydrogenase modified by 4-hydroxy-2-nonenal and metal-catalyzed oxidation to proteolysis by the multicatalytic protease. Archives of Biochemistry and Biophysics 311, 168-73.
Furukawa S., Fujita T., Shimabukuro M., Iwaki M., Yamada Y., Nakajima Y., Nakayama O., Makishima M., Matsuda M. and Shimomura I., 2004. Increased oxidative stress in obesity and its impact on metabolic syndrome. Journal of Clinical
Investigation 114, 1752-1761.
Gagnon A. and Sorisky A., 1998. The effect of glucose concentration on insulin-induced 3T3-L1 adipocytes cell differentiation. Obesity Research 6, 157-163.
Gaya M., Repetto V., Toneatto J., Anesini C., Piwien-Pilipuk G. and Moreno S., 2013.
Antiadipogenic effect of carnosic acid, a natural compound present in Rosmarinus officinalis, is exerted through the C/EBPs and PPARγ pathways at the onset of the differentiation program. Biochimica et Biophysica Acta 1830, 3796-3806.
Giugliano D., Ceriello A. and Paolisso G., 1996. Oxidative stress and diabetic vascular complications. Diabetes care 19, 257-67.
Grattagliano I., Palmieri V. O., Portincasa P., Moschetta A. and Palasciano G., 2008. Oxidative stress-induced risk factors associated with the metabolic syndrome: a unifying hypothesis. The Journal of Nutritional Biochemistry 19, 491-504.
Green H. and Kehinde O., 1975. An established preadipose cell line and its differentiation in culture. II. Factors affecting the adipose conversion. Cell 5, 19-27.
Gregoire F. M., Smas C. M. and Sul H. S., 1998. Understanding adipocyte differentiation.Physiological Reviews 78, 783-809.
Grune T. and Davies K. J. A., 2003. The proteasomal system and HNE-modified proteins. Molecular Aspects of Medicine 24, 195-204. Hayes J. D., Flanagan J. U. and Jowsey I. R., 2005. Glutathione transferases. Annual review of pharmacology and toxicology 45, 51-88.
Hayes J. D. and McLellan L. I., 1999. Glutathione and glutathione-dependent enzymes represent a co-ordinately regulated defence against oxidative stress. Free Radical
Research 31, 273-300.
Houstis N., Rosen E. D. and Lander E. S., 2006. Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature 440, 944-8.
Hubatsch I., Mannervik B., Gao L., Roberts L. J., Chen Y. and Morrow J. D., 2002. The cyclopentenone product of lipid peroxidation, 15-A 2t -isoprostane (8-isoprostaglandin A 2 ), is efficiently conjugated with glutathione by human and
rat glutathione transferase A4-4. Chemical Research in Toxicology 15, 1114-1118.
Klemm D. J., Leitner J. W., Watson P., Nesterova A., Reusch J. E.-B., Goalstone M. L. and Draznin B., 2001. Insulin-induced adipocyte differentiation. The Journal of
Biological Chemistry 276, 28430-28435.
Kontogianni V. G., Tomic G., Nikolic I., Nerantzaki A. A., Sayyad N., Stosic-Grujicic S., Stojanovic I., Gerothanassis I. P. and Tzakos A. G., 2013. Phytochemical profile of Rosmarinus officinalis and Salvia officinalis extracts and correlation to their antioxidant and anti-proliferative activity. Food Chemistry 136, 120-129.
Kraemer F. B. and Shen W.-J., 2002. Hormone-sensitive lipase:control of intracellular tri-(di-)acylglycerol and cholesteryl ester hydrolysis. Journal of Lipid Research 43,
1585-1594.
Lafontan M. and Langin D., 2009. Lipolysis and lipid mobilization in human adipose tissue. Progress in Lipid Research 48, 275-297.
Lampidonis A. D., Rogdakis E., Voutsinas G. E. and Stravopodis D. J., 2011. The resurgence of hormone-sensitive lipase (HSL) in mammalian lipolysis. Gene 477, 1-11.
Langin D. and Arner P., 2006. Importance of TNFα and neutral lipases in human adipose tissue lipolysis. Trends in Endocrinology and Metabolism 17, 314-320.
Lefterova M. I. and Lazar M. A., 2009. New developments in adipogenesis. Trends in Endocrinology and Metabolism 20, 107-114.
Liu H.-W., Tsai Y.-T. and Chang S.-J., 2014. Toona sinensis leaf extract inhibits lipid accumulation through up-regulation of genes involved in lipolysis and fatty acid
oxidation in adipocytes. Journal of Agricultural and Food Chemistry 62, 5887-5896.
Lorente-Cebrian S., Bustos M., Marti A., Fernandez-Galilea M., Martinez J. A. and Moreno-Aliaga M. J., 2012. Eicosapentaenoic acid inhibits tumour necrosis
factor-alpha-induced lipolysis in murine cultured adipocytes. The Journal of Nutritional Biochemistry 23, 218-27.
Miller D. M., Singh I. N., Wang J. A. and Hall E. D., 2013. Administration of the Nrf2–ARE activators sulforaphane and carnosic acid attenuates 4-hydroxy-2-nonenal-induced mitochondrial dysfunction ex vivo. Free Radical
Biology and Medicine 57, 1-9.
Nagasaki H., Yoshimura T. and Aoki N., 2012. Real-time monitoring of inflammation status in 3T3-L1 adipocytes possessing a secretory gaussia luciferase gene under
the control of nuclear factor-kappa B response element. Biochemical and Biophysical Research Communications 420, 623-627.
O''Neill L. A. J. and Hardie D. G., 2013. Metabolism of inflammation limited by AMPK and pseudo-starvation. Nature 493, 346-355.
Pappa A., Chen C., Koutalos Y., Townsend A. J. and Vasiliou V., 2003. Aldh3a1 protects human corneal epithelial cells from ultraviolet- and 4-hydroxy-2-nonenal-induced oxidative damage. Free radical biology & medicine 34, 1178-89.
Patel Y. M. and Lane M. D., 2000. Mitotic clonal expansion during preadipocyte differentiation: calpain-mediated turnover of p27. The Journal of Biological Chemistry 275, 17653-17660.
Pennathur S. and Heinecke J. W., 2007. Mechanisms for oxidative stress in diabetic cardiovascular disease. Antioxidants & Redox Signaling 9, 955-69.
Plomgaard P., Fischer C. P., Ibfelt T., Pedersen B. K. and van Hall G., 2008. Tumor necrosis factor-alpha modulates human in vivo lipolysis. The Journal of Clinical
Endocrinology and Metabolism 93, 543-9.
Poli G., Schaur R. J., Siems W. G. and Leonarduzzi G., 2008. 4-hydroxynonenal: a membrane lipid oxidation product of medicinal interest. Medicinal Research
Reviews 28, 569-631.
Poulos S. P., Dodson M. V. and Hausman G. J., 2010. Cell line models for differentiation: preadipocytes and adipocytes. Experimental Biology and Medicine 235,
1185-1193.
Prieto D., Contreras C. and Sanchez A., 2014. Endothelial dysfunction, obesity and insulin resistance. Current Vascular Pharmacology 12, 412-26.
Qiang L. and Farmer S. R., 2006. C/EBPα-dependent induction of glutathione S-transferase/maleylacetoacetate isomerase (GSTf/MAAI) expression during the differentiation of mouse fibroblasts into adipocytes. Biochemical and Biophysical
Research Communications 340, 845–851.
Rayalam S., Della-Fera M. A. and Baile C. A., 2008. Phytochemicals and regulation of the adipocyte life cycle. Journal of Nutritional Biochemistry 19, 717-726.
Roede J. R. and Jones D. P., 2010. Reactive species and mitochondrial dysfunction: mechanistic significance of 4-hydroxynonenal. Environmental and Molecular
Mutagenesis 51, 380-390.
Russell A. P., Gastaldi G., Bobbioni-Harsch E., Arboit P., Gobelet C., Deriaz O., Golay A., Witztum J. L. and Giacobino J. P., 2003. Lipid peroxidation in skeletal muscle of
obese as compared to endurance-trained humans: a case of good vs. bad lipids?
FEBS Letters 551, 104-6.
Ryden M., Dicker A., van Harmelen V., Hauner H., Brunnberg M., Perbeck L., Lonnqvist F. and Arner P., 2002. Mapping of early signaling events in tumor necrosis factor-alpha-mediated lipolysis in human fat cells. The Journal of Biological Chemistry 277, 1085-91.
Schwarz K. and Ternes W., 1992. Antioxidative constituents of Rosmarinus officinalis and Salvia officinalis. isolation of carnosic acid and formation of other phenolic diterpenes. Zeitschrift fur Lebensmittel-Untersuchung und -Forschung 195, 99-103.
Sharda P. Singh, Maciej Niemczyk, Ludwika Zimniak and Piotr Zimniak, 2009. Fat accumulation in Caenorhabditis elegans triggered by the electrophilic lipid peroxidation product 4‐hydroxynonenal (4‐HNE) Aging 1, 68-80.
Sherratt P. J. and Hayes J. D., 2002. Glutathione S-transferases. Enzyme Systems that Metabolise Drugs and Other Xenobiotics., 319-352.
Shringarpure R., Grune T., Sitte N. and Davies K. J., 2000. 4-Hydroxynonenal-modified amyloid-beta peptide inhibits the proteasome: possible importance in Alzheimer''s
disease. Cell and Molecular Life Sciences 57, 1802-9.
Singh S. P., Niemczyk M., Saini D., Awasthi Y. C., Zimniak L. and Zimniak P., 2008.
Role of the electrophilic lipid peroxidation product 4-hydroxynonenal in the development and maintenance of obesity in mice. Biochemistry 47, 3900-3911.
Souza S. C., de Vargas L. M., Yamamoto M. T., Lien P., Franciosa M. D., Moss L. G. and Greenberg A. S., 1998. Overexpression of perilipin A and B blocks the ability of
tumor necrosis factor alpha to increase lipolysis in 3T3-L1 adipocytes. The Journal of Biological Chemistry 273, 24665-9.
Steinberg G. R., 2009. Role of the AMP-activated protein kinase in regulating fatty acid metabolism during exercise. Applied Physiology, Nutrition, and Metabolism 34, 315-322.
Takahashi T., Tabuchi T., Tamaki Y., Kosaka K., Takikawa Y. and Satoh T., 2009.
Carnosic acid and carnosol inhibit adipocyte differentiation in mouse 3T3-L1 cells through induction of phase 2 enzymes and activation of glutathione metabolism. Biochemical and Biophysical Research Communications 382, 549–554.
Tang Q. Q. and Lane M. D., 2012. Adipogenesis:from stem cell to adipocyte. Annual Review of Biochemistry 81, 715-736.
Toit E. F. d. and Donner D. G., 2012. Myocardial insulin resistance: an overview of its causes, effects, and potential therapy. Llicensee InTech ,189-226.
Tomanek R. J., Christensen L. P., Simons M., Murakami M., Zheng W. and Schatteman G. C., 2010. Embryonic coronary vasculogenesis and angiogenesis are regulated by
interactions between multiple FGFs and VEGF and are infuenced by mesenchymal stem cells. Delelopmental Dynamics 239, 3182–3191.
Tsai C.-W., Liu K.-L., Lin Y.-R. and Kuo W.-C., 2014. The mechanisms of carnosic acid attenuates tumor necrosis factor-alpha-mediated inflammation and insulin resistance in 3T3-L1 adipocytes. Molecular Nutrition & Food Research 58,
654-664.
Vincent H. K., Powers S. K., Dirks A. J. and Scarpace P. J., 2001. Mechanism for obesity-induced increase in myocardial lipid peroxidation. International Journal of Obesity Related Metabolic Disorders 25, 378-88.
Wang T., Takikawa Y., Tabuchi T., Satoh T., Kosaka K. and Suzuki K., 2012a. Carnosic acid (CA) prevents lipid accumulation in hepatocytes through the EGFR/MAPK
pathway. Journal of Gastroenterology 47, 805-813.
Wang Z., Dou X., Gu D., Shen C., Yao T., Nguyen V., Braunschweig C. and Song Z., 2012b. 4-Hydroxynonenal differentially regulates adiponectin gene expression
and secretion via activating PPARγ and accelerating ubiquitin–proteasome degradation. Molecular and Cellular Endocrinology, 222-231.
Watt M. J., 2009. Triglyceride lipases alter fuel metabolism and mitochondrial gene expression. Applied Physiology, Nutrition, and Metabolism 34, 340-347.
Xiang Q., Liu Z., Wang Y., Xiao H., Wu W., Xiao C. and Liu X., 2013. Carnosic acid attenuates lipopolysaccharide-induced liver injury in rats via fortifying cellular
antioxidant defense system. Food and Chemical Toxicology 53, 1-9.
Xiao-yun Xie, Kong P.-R., Wu J.-f., Li Y. and Li Y.-x., 2012. Curcumin attenuates lipolysis stimulated by tumor necrosis factor-alpha or isoproterenol in 3T3-L1
adipocytes. Phytomedicine 20, 3-8. Xu S., Yang G., Yang M., Li S., Liu H. and Li L., 2011. Elevated adipose triglyceride
lipase in newly diagnosed type 2 diabetes mellitus with hypertension. The American Journal of the Medical Sciences 342, 452-455.
Yang X., Zhang X., Heckmann B. L., Lu X. and Liu J., 2011. Relative contribution of adipose triglyceride lipase and hormone-sensitive lipase to tumor necrosis factor-alpha(TNF-alpha)-induced lipolysis in adipocytes. Journal of Biological Chemistry 286, 40477-40485.
Zechner R., Kienesberger P. C., Haemmerle G., Zimmermann R. and Lass A., 2009.
Adipose triglyceride lipase and the lipolytic catabolism of cellular fat stores. Journal of Lipid Research 50, 3-21.
Zechner R., Zimmermann R., Eichmann T. O., Kohlwein S. D., Haemmerle G., Lass A. and Madeo F., 2012. Fat signals-lipases and lipolysis in lipid metabolism and
signaling. Cell Metabolism 15, 279-91.
Zhang H. H., Halbleib M., Ahmad F., Manganiello V. C. and Greenberg A. S., 2002. Tumor necrosis factor-alpha stimulates lipolysis in differentiated human
adipocytes through activation of extracellular signal-related kinase and elevation of intracellular cAMP. Diabetes 51, 2929-2935.
Zhang X., Wang Z., Li J., Gu D., Li S., Shen C. and Song Z., 2013. Increased 4-Hydroxynonenal formation contributes to obesity-related lipolytic activation in adipocytes. PLOS one 8, 1-10.
Zimmermann R., Lass A., Haemmerle G. and Zechner R., 2009. Fate of fat: the role of adipose triglyceride lipase in lipolysis. Biochimica et Biophysica Acta 1791, 494-500.