臺灣博碩士論文加值系統

胰島素阻抗所引起的血壓增高、血脂異常、糖代謝失調為造成代謝症候群的主要發病機制。在胰島素調控的組織中，肝臟為主要調控醣類及脂質代謝的組織。研究指出，香椿對於治療代謝症候群有益，然而香椿對肝臟代謝調控的功能仍然不明瞭。本研究中，使用了二維電泳及西方墨點法來探討香椿醇萃物對高隻飼料餵食小鼠的影響。並分別使用線粒體膜電位及油紅染色來判斷抗氧化活性及降低脂質堆積的效果。經由2D及mass的鑑定，發現了餵食香椿醇萃物的HFD小鼠相較於HFD小鼠，在氧化壓力相關蛋白及脂質代謝相關蛋白的表現上有顯著的差異。HFD上调山梨醇脱氢酶（SDH），UDP-葡萄糖的脱氢酶（UDGH），谷氨酸脱氢酶（GDH）蛋白表达的建议，HFD增加的小鼠肝脏糖异生。在另一方面，HFD + TSL-E抑制糖原异生增加，GDH的蛋白的表达下降，磷酸烯醇式丙酮酸羧2（PCK2）证实了，恢复的SDH，UDGH HFD。虽然HFD70 kDa的热休克蛋白（HSP70），过氧化氢酶（CAT），HSPd1增加和减少过氧化物酶（PRDX6）蛋白的表达，HFD+ TSL-E增加PRDX6和恢复HSP70，Hspd1和猫的蛋白表达，表示，TSL-E表现出抗氧化活性。 Luciferase report assay的結果顯示香椿醇萃物具有活化PPARα及PPARγ，且在動物實驗種也發現香椿純萃物會增加HFD小鼠肝臟PPARα及PPARγ的表現。
在HFD小鼠中，餵食香椿醇萃物會降低氧化壓力及抑制多元醇路徑(polyol pathway) 的活化，且會經由活化PPARα及PPARγ改善血脂異常

The major pathogenesis of metabolic syndrome is the development of insulin resistance, which promotes the elevation of blood pressure, dyslipidemia, and dysregulation of glucose metabolism. Among the target tissues of insulin, liver is the principal regulator of glucose and lipid metabolism by controlling hepatic glucose production, glycogen storage and lipogenesis. Toona sinnesis (TS) has been reported to be beneficial for metabolic syndrome, however the effect of TS on liver metabolism is not clear. In the present study, proteomics analysis and Western blot were used to investigate the effect of TSL-E on the high-fat diet (HFD) fed mice. The anti-oxidation activity and lipid lowering effect were investigated by measurement of mitochondria membrane potential (MMP) and Oil-red-O staining. Using the 2D-gel proteomic analysis followed by mass spectrometry identification, we found a clear distinction in differential expression of oxidative stress, glucose metabolism and lipid metabolism related proteins responding TSL-E. HFD up regulated sorbitol dehydrogenase (SDH), UDP-6 glucose dehydrogenase (UDGH), glutamate dehydrogenase (GDH) proteins expression suggested that HFD increased gluconeogenesis in liver of mice. In the other hand, HFD+TSL-E inhibited the increasing of gluconeogenesis in HFD by restored SDH, UDGH, GDH protein expression that were confirmed by decreased of phosphoenolpyruvate carboxykinase 2 (PCK2). While HFD increased heat shock protein 70 kda (HSP70), Catalase (Cat), HSPd1 and decreased peroxiredoxin 6 (Prdx6) proteins expression, HFD+TSL-E increased Prdx6 and restored HSP70, Hspd1 and Cat proteins expression, indicated that TSL-E exhibited anti-oxidant activity. TSL-E also shown high peroxisome proliferator-activated receptor alpha/gamma (PPARalpha/gamma)-dependent luciferase activity that confirmed by increased the expression of PPARalpha/gamma in liver of HFD mice treated with TSL-E. In conclusion, TSL-E improved the dyslipidemia of high fat diet mice through activation of PPARalpha/gamma, reduction of oxidative stress and decreasing gluconeogenesis by inhibition of the activation of the polyol pathway

Abstract iii
中文摘要 v
Acknowledgement vii
Contents viii
List of Tables xi
Chapter 1 Introduction 1
1.1 Toona sinensis 1
1.2 Mechanisms and complications of Metabolic syndrome 2
1.3 Peroxisome Proliferator-Activated Receptors (PPAR) 6
1.4 Liver metabolism 8
1.4.1 Hepatic glucose metabolism 8
1.4.2 Hepatic lipid metabolism 9
1.4.3 Hepatic glycogen metabolism 10
1.4.4 Fatty acid oxidation 11
1.5 The high fat diet model 12
1.6 The polyol pathway 14
1.7 Effects of oleic acid in hepatocytes metabolism 15
1.8 Mechanic generation of reactive oxygen species (ROS) 16
1.9 Rationale 18
Chapter 2 Material and Method 20
2.1 Material 20
2.1.1 Common chemical use 20
2.1.2 Antibodies 21
2.1.3 Equipments and machines 22
2.1.4 Animal 22
2.1.5 Cell culture 25
2.1.6 TSL-E extract 25
2.2 Method 26
2.2.1 Western Blot 26
2.2.2 Two-dimensions electrophoresis 29
2.2.3 Oil red O staining 34
2.2.4 Flow cytometer detect Mitochondrial Membrane Potential 35
Chapter 3 Results 36
3.1 Effects of TSL-E on body weight, triglyceride content, serum cholesterol and serum glucose in high fat diet mice 36
3.2 Proteomic profiling of TSL-E regulated protein on liver of high fat diet mice 36
3.3 Effect of high fat diet on liver metabolism 37
3.4 The effects of TSL-E on liver metabolism of high fat diet mice 38
3.5 Effects of TSL-E on PPARalpha, PPARgamma, PCK2 and HMG-CoA protein expression in liver of mice 39
3.6 TSL-E exhibited both PPARalpha and PPARgamma ligand binding activity 41
3.7 Effect of TSL-E on lipid accumulation induced by oleic acid 41
3.8 Effect of TSL-E on mitochondria membrane potential of HepG2 induced oxidative stress by oleic acid 42
Chapter 4 Discussion 44
4.1 TSL-E improved liver metabolism by suppressed the elevated of gluconeogenesis and increased lipolysis in liver of high fat diet mice 44
4.2 TSL-E decreased oxidative stress in liver of high fat diet mice 49
4.3 TSL-E activated the protein kinase C –lambda in high fat diet mice 54
4.4 Proposed pathway of the effects of TSL-E liver of high fat diet mice 55
References 59
Appendixes 92
Mascot search result 92

Abranches, M. V., de Oliveira, F. C. E., ＆ Bressan, J. (2011). Peroxisome proliferator-activated receptor: effects on nutritional homeostasis, obesity and diabetes mellitus. Nutricion Hospitalaria, 26(2), 271-279.
Ahmed, I., ＆ Goldstein, B. J. (2006). Cardiovascular risk in the spectrum of type 2 diabetes mellitus. Mount Sinai Journal of Medicine, 73(5), 759-768.
Arner, P. (2002). Insulin resistance in type 2 diabetes: role of fatty acids. Diabetes-Metabolism Research and Reviews, 18, S5-S9.
Assumpcao, C. R. L., Brunini, T. M. C., Pereira, N. R., Godoy-Matos, A. F., Siqueira, M. A. S., Mann, G. E., ＆ Mendes-Ribeiro, A. C. (2010). Insulin resistance in obesity and metabolic syndrome: Is there a connection with platelet L-arginine transport? Blood Cells Molecules and Diseases, 45(4), 338-342.
Atshaves, B. P., Martin, G. G., Hostetler, H. A., McIntosh, A. L., Kier, A. B., ＆ Schroeder, F. (2010). Liver fatty acid-binding protein and obesity. Journal of Nutritional Biochemistry, 21(11), 1015-1032.
Avramoglu, R. K., Qiu, W., ＆ Adeli, K. (2003). Mechanisms of metabolic dyslipidemia in insulin resistant states: Deregulation of hepatic and intestinal lipoprotein secretion. Frontiers in Bioscience, 8, D464-D476.
Barcelo, A., Pierola, J., de la Pena, M., Esquinas, C., Fuster, A., Sanchez-de-la-Torre, M., Carrera, M., Alonso-Fernandez, A., Ladaria, A., Bosch, M., ＆ Barbe, F. (2011). Free fatty acids and the metabolic syndrome in patients with obstructive sleep apnoea. European Respiratory Journal, 37(6), 1418-1423.
Baron, M., Leroyer, A. S., Majd, Z., Lalloyer, F., Vallez, E., Bantubungi, K., Chinetti-Gbaguidi, G., Delerive, P., Boulanger, C. M., Staels, B., ＆ Tailleux, A. (2011). PPAR alpha activation differently affects microparticle content in atherosclerotic lesions and liver of a mouse model of atherosclerosis and NASH. Atherosclerosis, 218(1), 69-76.
Bechmann, L. P., Hannivoort, R. A., Gerken, G., Hotamisligil, G. S., Trauner, M., ＆ Canbay, A. (2012). The interaction of hepatic lipid and glucose metabolism in liver diseases. Journal of Hepatology, 56(4), 952-964.
Beeson, M., Sajan, M. P., Dizon, M., Grebenev, D., Gomez-Daspet, J., Miura, A., Kanoh, Y., Powe, J., Bandyopadhyay, G., Standaert, M. L., ＆ Farese, R. V. (2003). Activation of protein kinase C-zeta by insulin and phosphatidylinositol-3,4,5-(PO4)3 is defective in muscle in type 2 diabetes and impaired glucose tolerance: amelioration by rosiglitazone and exercise. Diabetes, 52(8), 1926-1934.
Beguinot, F., ＆ Formisano, P. (2008). Atypical protein kinase C dysfunction and the metabolic syndrome. Trends Endocrinol Metab, 19(2), 39-41.
Caballero, M. J., Izquierdo, M. S., Kjorsvik, E., Fernandez, A. J., ＆ Rosenlund, G. (2004). Histological alterations in the liver of sea bream, Sparus aurata L., caused by short- or long-term feeding with vegetable oils. Recovery of normal morphology after feeding fish oil as the sole lipid source. Journal of Fish Diseases, 27(9), 531-541.
Caglayan, E., Blaschke, F., Takata, Y., ＆ Hsueh, W. A. (2005). Metabolic syndrome-interdependence and metabolic pathways. Current Opinion in Pharmacology, 5(2), 135-142.
Cai, E. P., ＆ Lin, J. K. (2009). Epigallocatechin Gallate (EGCG) and Rutin Suppress the Glucotoxicity through Activating IRS2 and AMPK Signaling in Rat Pancreatic beta Cells. Journal of Agricultural and Food Chemistry, 57(20), 9817-9827.
Carbone, V., Zhao, H. T., Chung, R., Endo, S., Hara, A., ＆ El-Kabbani, O. (2009). Correlation of binding constants and molecular modelling of inhibitors in the active sites of aldose reductase and aldehyde reductase. Bioorganic ＆ Medicinal Chemistry, 17(3), 1244-1250.
Catov, J. M., Bodnar, L. M., Ness, R. B., Barron, S. J., ＆ Roberts, J. M. (2007). Inflammation and dyslipidemia related to risk of spontaneous preterm birth. American Journal of Epidemiology, 166(11), 1312-1319.
Chang, H. L., Hsu, H. K., Su, J. H., Wang, P. H., Chung, Y. F., Chia, Y. C., Tsai, L. Y., Wu, Y. C., ＆ Yuan, S. S. F. (2006). The fractionated Toona sinensis leaf extract induces apoptosis of human ovarian cancer cells and inhibits tumor growth in a murine xenograft model. Gynecologic Oncology, 102(2), 309-314.
Chao, C. Y., Mong, M. C., Chan, K. C., ＆ Yin, M. C. (2010). Anti-glycative and anti-inflammatory effects of caffeic acid and ellagic acid in kidney of diabetic mice. Molecular Nutrition ＆ Food Research, 54(3), 388-395.
Chen, C. J., Michaelis, M., Hsu, H. K., Tsai, C. C., Yang, K. D., Wu, Y. C., Cinatl, J., ＆ Doerr, H. W. (2008). Toona sinensis Roem tender leaf extract inhibits SARS coronavirus replication. Journal of Ethnopharmacology, 120(1), 108-111.
Chen, H. M., Wu, Y. C., Chia, Y. C., Chang, F. R., Hsu, H. K., Hsieh, Y. C., Chen, C. C., ＆ Yuan, S. S. (2009). Gallic acid, a major component of Toona sinensis leaf extracts, contains a ROS-mediated anti-cancer activity in human prostate cancer cells. Cancer Letters, 286(2), 161-171.
Chen, H. Y., Lin, Y. C., ＆ Hsieh, C. L. (2007). Evaluation of antioxidant activity of aqueous extract of some selected nutraceutical herbs. Food Chemistry, 104(4), 1418-1424.
Commerford, S. R., Ferniza, J. B., Bizeau, M. E., Thresher, J. S., Willis, W. T., ＆ Pagliassotti, M. J. (2002). Diets enriched in sucrose or fat increase gluconeogenesis and G-6-Pase but not basal glucose production in rats. Am J Physiol Endocrinol Metab, 283(3), E545-555.
Cong, W. N., Tao, R. Y., Tian, J. Y., Liu, G. T., ＆ Ye, F. (2008). The establishment of a novel non-alcoholic steatohepatitis model accompanied with obesity and insulin resistance in mice. Life Sciences, 82(19-20), 983-990.
Corl, B. A., Oliver, S. A. M., Lin, X., Oliver, W. T., Ma, Y., Harrell, R. J., ＆ Odle, J. (2008). Conjugated linoleic acid reduces body fat accretion and lipogenic gene expression in, neonatal pigs fed low- or high-fat formulas. Journal of Nutrition, 138(3), 449-454.
Crabb, D. W., Matsumoto, M., Chang, D., ＆ You, M. (2004). Overview of the role of alcohol dehydrogenase and aldehyde dehydrogenase and their variants in the genesis of alcohol-related pathology. Proceedings of the Nutrition Society, 63(01), 49-63.
Cui, J., Xiao, Y., Shi, Y. H., Wang, B., ＆ Le, G. W. (2012). Lipoic acid attenuates high-fat-diet-induced oxidative stress and B-cell-related immune depression. Nutrition, 28(3), 275-280.
de Haan, J. B., Witting, P. K., Stefanovic, N., Pete, J., Daskalakis, M., Kola, I., Stocker, R., ＆ Smolich, J. J. (2006). Lack of the antioxidant glutathione peroxidase-1 does not increase atherosclerosis in C57BL/J6 mice fed a high-fat diet. Journal of Lipid Research, 47(6), 1157-1167.
Dunn, F. L., Higgins, L. S., Fredrickson, J., DePaoli, A. M., ＆ Grp, I.-. (2011). Selective modulation of PPAR gamma activity can lower plasma glucose without typical thiazolidinedione side-effects in patients with Type 2 diabetes. Journal of Diabetes and Its Complications, 25(3), 151-158.
Eaton, S., Bartlett, K., ＆ Pourfarzam, M. (1996). Mammalian mitochondrial beta-oxidation. Biochemical Journal, 320, 345-357.
Eisenste.Ab, Strack, I., ＆ Steiner, A. (1973). Effects of a High Fat, Carbohydrate-Free Diet on Gluconeogenesis in Rat-Liver. American Journal of Clinical Nutrition, 26(7), R19-R19.
Eisenste.Ab, Strack, I., ＆ Steiner, A. (1974). Increased Hepatic Gluconeogenesis without a Rise of Glucagon-Secretion in Rats Fed a High Fat Diet. Diabetes, 23(11), 869-875.
Fahien, L. A., ＆ MacDonald, M. J. (2011). The Complex Mechanism of Glutamate Dehydrogenase in Insulin Secretion. Diabetes, 60(10), 2450-2454.
Fan, S., Chen, H. N., Wang, C. J., Tseng, W. C., Hsu, H. K., ＆ Weng, C. F. (2007). Toona sinensis Roem (Meliaceae) leaf extract alleviates liver fibrosis via reducing TGFPI and collagen. Food and Chemical Toxicology, 45(11), 2228-2236.
Garratt, E., Vickers, M., Gluckman, P., Hanson, M., Burdge, G., ＆ Lillycrop, K. (2011). Leptin and PPAR alpha: Understanding Their Role in Preventing Obesity in the IUGR Rat. Journal of Developmental Origins of Health and Disease, 2, S28-S28.
Gillespie, W., Tyagi, N., ＆ Tyagi, S. C. (2011). Role of PPAR gamma, a Nuclear Hormone Receptor in Neuroprotection. Indian Journal of Biochemistry ＆ Biophysics, 48(2), 73-81.
Girard, J. (1993). Gluconeogenesis - a Crucial Metabolic Pathway for Neonatal Glucose-Homeostasis. M S-Medecine Sciences, 9(3), 297-306.
Gomez-Lechon, M. J., Donato, M. T., Martinez-Romero, A., Jimenez, N., Castell, J. V., ＆ O'Connor, J. E. (2007). A human hepatocellular in vitro model to investigate steatosis. Chemico-Biological Interactions, 165(2), 106-116.
Hashimoto, N., Kido, Y., Uchida, T., Matsuda, T., Suzuki, K., Inoue, H., Matsumoto, M., Ogawa, W., Maeda, S., Fujihara, H., Ueta, Y., Uchiyama, Y., Akimoto, K., Ohno, S., Noda, T., ＆ Kasuga, M. (2005). PKClambda regulates glucose-induced insulin secretion through modulation of gene expression in pancreatic beta cells. Journal of Clinical Investigation, 115(1), 138-145.
Hojka, A., ＆ Rapak, A. (2011). Peroxisome proliferator-activated receptors (PPAR). Antiproliferative properties. Postepy Higieny I Medycyny Doswiadczalnej, 65, 404-413.
Hsieh, C. L., Lin, Y. C., Ko, W. S., Peng, C. H., Huang, C. N., ＆ Peng, R. Y. (2005). Inhibitory effect of some selected nutraceutic herbs on LDL glycation induced by glucose and glyoxal. Journal of Ethnopharmacology, 102(3), 357-363.
Hu, X. Y., Fang, Q., Wang, J. S., Xie, J. Q., Chai, B. S., Li, F. Q., Cui, X., ＆ Yang, Y. A. (2011). Over-expression of aldehyde dehydrogenase-2 protects against H(2)O(2)-induced oxidative damage and apoptosis in peripheral blood mononuclear cells. Acta Pharmacologica Sinica, 32(2), 245-252.
Huang, H. J., Lee, K. J., Yu, H. W., Chen, H. Y., Tsai, F. J., ＆ Chen, C. Y. C. (2010). A Novel Strategy for Designing the Selective PPAR Agonist by the Sum of Activity Model. Journal of Biomolecular Structure ＆ Dynamics, 28(2), 187-200.
Hulsmans, M., Van Dooren, E., ＆ Holvoet, P. (2012). Mitochondrial Reactive Oxygen Species and Risk of Atherosclerosis. Current Atherosclerosis Reports, 14(3), 264-276.
Islam, M. S., ＆ Loots, D. T. (2009). Experimental Rodent Models of Type 2 Diabetes: A Review. Methods and Findings in Experimental and Clinical Pharmacology, 31(4), 249-261.
Janesick, A., ＆ Blumberg, B. (2011). Minireview: PPAR gamma as the target of obesogens. Journal of Steroid Biochemistry and Molecular Biology, 127(1-2), 4-8.
Jang, S. M., Kim, M. J., Choi, M. S., Kwon, E. Y., ＆ Lee, M. K. (2010). Inhibitory effects of ursolic acid on hepatic polyol pathway and glucose production in streptozotocin-induced diabetic mice. Metabolism-Clinical and Experimental, 59(4), 512-519.
Jeng, J. H., Wang, Y. J., Chang, W. H., Wu, H. L., Li, C. H., Uang, B. J., Kang, J. J., Lee, J. J., Hahn, L. J., Lin, B. R., ＆ Chang, M. C. (2004). Reactive oxygen species are crucial for hydroxychavicol toxicity toward KB epithelial cells. Cellular and Molecular Life Sciences, 61(1), 83-96.
Jia, L., Ma, Y. Y., Rong, S. X., Betters, J. L., Xie, P., Chung, S., Wang, N. P., Tang, W. Q., ＆ Yu, L. Q. (2010). Niemann-Pick C1-Like 1 deletion in mice prevents high-fat diet-induced fatty liver by reducing lipogenesis. Journal of Lipid Research, 51(11), 3135-3144.
Jiang, M., Strand, D. W., Franco, O. E., Clark, P. E., ＆ Hayward, S. W. (2011). PPAR gamma: A molecular link between systemic metabolic disease and benign prostate hyperplasia. Differentiation, 82(4-5), 220-236.
Johnson, D. T., Harris, R. A., French, S., Aponte, A., ＆ Balaban, R. S. (2010). Proteomic changes associated with diabetes in the BB-DP rat. (vol 296, E422, 2009). American Journal of Physiology-Endocrinology and Metabolism, 298(4), E895-E895.
Jump, D. B. (2011). Fatty acid regulation of hepatic lipid metabolism. Current Opinion in Clinical Nutrition and Metabolic Care, 14(2), 115-120.
Kanoh, Y., Bandyopadhyay, G., Sajan, M. P., Standaert, M. L., ＆ Farese, R. V. (2001). Rosiglitazone, insulin treatment, and fasting correct defective activation of protein kinase C-zeta/lambda by insulin in vastus lateralis muscles and adipocytes of diabetic rats. Endocrinology, 142(4), 1595-1605.
Kanoh, Y., Sajan, M. P., Bandyopadhyay, G., Miura, A., Standaert, M. L., ＆ Farese, R. V. (2003). Defective activation of atypical protein kinase C zeta and lambda by insulin and phosphatidylinositol-3,4,5-(PO4)(3) in skeletal muscle of rats following high-fat feeding and streptozotocin-induced diabetes. Endocrinology, 144(3), 947-954.
Keating, G. M. (2011). Fenofibrate A Review of its Lipid-Modifying Effects in Dyslipidemia and its Vascular Effects in Type 2 Diabetes Mellitus. American Journal of Cardiovascular Drugs, 11(4), 227-247.
Kim, H. J., Takahashi, M., ＆ Ezaki, O. (1999). Fish oil feeding decreases mature sterol regulatory element-binding protein 1 (SREBP-1) by down-regulation of SREBP-1c mRNA in mouse liver - A possible mechanism for down-regulation of lipogenic enzyme mRNAs. Journal of Biological Chemistry, 274(36), 25892-25898.
Kim, J. H., Kim, D., Kim, J., ＆ Hwang, J. K. (2011). Euchresta horsfieldii Benn. activates peroxisome proliferator-activated receptor alpha and regulates expression of genes involved in fatty acid metabolism in human HepG2 cells. Journal of Ethnopharmacology, 133(1), 244-247.
Kotake, Y., Kishida, H., Nakae, D., ＆ Floyd, R. A. (2002). A flow cytometry study on nitric oxide and ROS formation in primary hepatocytes isolated from rats fed with an amino acid diet. Free Radical Biology and Medicine, 33, S260-S260.
Kurokawa, M., Hirano, T., Furukawa, S., Nagano, S., ＆ Adachi, M. (1995). Similar to Oleic-Acid, Eicosapentaenoic Acid Stimulates Apolipoprotein-B Secretion by Inhibiting Its Intracellular Degradation in Hep G2 Cells. Atherosclerosis, 112(1), 59-68.
Lann, D., ＆ LeRoith, D. (2007). Insulin resistance as the underlying cause for the metabolic syndrome. Medical Clinics of North America, 91(6), 1063-+.
Lechleitner, M. (2008). Obesity and the Metabolic Syndrome in the Elderly - A Mini-Review. Gerontology, 54(5), 253-259.
Lin, C. Y., Tsai, S. J., Huang, C. S., ＆ Yin, M. C. (2011). Antiglycative Effects of Protocatechuic Add in the Kidneys of Diabetic Mice. Journal of Agricultural and Food Chemistry, 59(9), 5117-5124.
Lopes, J. P., Oliveira, S. M., ＆ Fortunato, J. S. (2008). OXIDATIVE STRESS AND ITS EFFECTS ON INSULIN RESISTANCE AND PANCREATIC beta-CELLS DYSFUNCTION Relationship with Type 2 Diabetes Mellitus Complications. Acta Medica Portuguesa, 21(3), 293-302.
McKeage, K., ＆ Keating, G. M. (2011). Fenofibrate A Review of its Use in Dyslipidaemia. Drugs, 71(14), 1917-1946.
Mei, S., Ni, H. M., Manley, S., Bockus, A., Kassel, K. M., Luyendyk, J. P., Copple, B. L., ＆ Ding, W. X. (2011). Differential Roles of Unsaturated and Saturated Fatty Acids on Autophagy and Apoptosis in Hepatocytes. Journal of Pharmacology and Experimental Therapeutics, 339(2), 487-498.
Monsenego, J., Mansouri, A., Akkaoui, M., Lenoir, V., Esnous, C., Fauveau, V., Tavernier, V., Girard, J., ＆ Prip-Buus, C. (2012). Enhancing liver mitochondrial fatty acid oxidation capacity in obese mice improves insulin sensitivity independently of hepatic steatosis. Journal of Hepatology, 56(3), 632-639.
Mu, R. M., Wang, X. R., Liu, S. X., Yuan, X. L., Wang, S. B., ＆ Fan, Z. Q. (2007). Rapid determination of volatile compounds in Toona sinensis (A. Juss.) Roem. by MAE-HS-SPME followed by GC-MS. Chromatographia, 65(7-8), 463-467.
Nagai, H., Ebisu, S., Abe, R., Goto, T., Takahashi, N., Hosaka, T., ＆ Kawada, T. (2011). Development of a Novel PPAR gamma Ligand Screening System Using Pinpoint Fluorescence-Probed Protein. Bioscience Biotechnology and Biochemistry, 75(2), 337-341.
Newberry, E. P., Kennedy, S. M., Xie, Y., Sternard, B. T., Luo, J. Y., ＆ Davidson, N. O. (2008). Diet-induced obesity and hepatic steatosis in L-Fabp(-/-) mice is abrogated with SF, but not PUFA, feeding and attenuated after cholesterol supplementation. American Journal of Physiology-Gastrointestinal and Liver Physiology, 294(1), G307-G314.
Newsholme, P., Haber, E. P., Hirabara, S. M., Rebelato, E. L. O., Procopio, J., Morgan, D., Oliveira-Emilio, H. C., Carpinelli, A. R., ＆ Curi, R. (2007). Diabetes associated cell stress and dysfunction: role of mitochondrial and non-mitochondrial ROS production and activity. The Journal of Physiology, 583(1), 9-24.
Nguyen, P., Leray, V., Diez, M., Serisier, S., Le Bloc'h, J., Siliart, B., ＆ Dumon, H. (2008). Liver lipid metabolism. Journal of Animal Physiology and Animal Nutrition, 92(3), 272-283.
Nishikawa, T., ＆ Araki, E. (2007). Impact of mitochondrial ROS production in the pathogenesis of diabetes mellitus and its complications. Antioxidants ＆ Redox Signaling, 9(3), 343-353.
Niu, Y., Li, S., Na, L., Feng, R., Liu, L., Li, Y., ＆ Sun, C. (2012). Mangiferin Decreases Plasma Free Fatty Acids through Promoting Its Catabolism in Liver by Activation of AMPK. Plos One, 7(1), e30782.
Nogueiras, R., Lopez, M., ＆ Dieguez, C. (2010). Regulation of lipid metabolism by energy availability: a role for the central nervous system. Obesity Reviews, 11(3), 185-201.
Novak, E. M., Keller, B. O., ＆ Innis, S. M. (2012). Metabolic development in the liver and the implications of the n-3 fatty acid supply. American Journal of Physiology-Gastrointestinal and Liver Physiology, 302(2), G250-G259.
Nuernberg, K., Breier, B. H., Jayasinghe, S. N., Bergmann, H., Thompson, N., Nuernberg, G., Dannenberger, D., Schneider, F., Renne, U., Langhammer, M., ＆ Huber, K. (2011). Metabolic responses to high-fat diets rich in n-3 or n-6 long-chain polyunsaturated fatty acids in mice selected for either high body weight or leanness explain different health outcomes. Nutrition ＆ Metabolism, 8.
Ohmura, C., Watada, H., Azuma, K., Shimizu, T., Kanazawa, A., Ikeda, F., Yoshihara, T., Fujitani, Y., Hirose, T., Tanaka, Y., ＆ Kawamori, R. (2009). Aldose Reductase Inhibitor, Epalrestat, Reduces Lipid Hydroperoxides in Type 2 Diabetes. Endocrine Journal, 56(1), 149-156.
Oosterveer, M. H., van Dijk, T. H., Tietge, U. J. F., Boer, T., Havinga, R., Stellaard, F., Groen, A. K., Kuipers, F., ＆ Reijngoud, D.-J. (2009). High Fat Feeding Induces Hepatic Fatty Acid Elongation in Mice. Plos One, 4(6), e6066.
Panchal, S. K., ＆ Brown, L. (2011). Rodent Models for Metabolic Syndrome Research. Journal of Biomedicine and Biotechnology.
Pei-Hwei, W., Tsai, M. J., Hsu, C. Y., Wang, C. Y., Hsu, H. K., ＆ Weng, C. F. (2008). Toona sinensis Roem (Meliaceae) leaf extract alleviates hyperglycemia via altering adipose glucose transporter 4. Food and Chemical Toxicology, 46(7), 2554-2560.
Perl, A. (2007). The pathogenesis of transaldolase deficiency. Iubmb Life, 59(6), 365-373.
Perl, A., Hanczko, R., Telarico, T., Oaks, Z., ＆ Landas, S. (2011). Oxidative stress, inflammation and carcinogenesis are controlled through the pentose phosphate pathway by transaldolase. Trends in Molecular Medicine, 17(7), 395-403.
Poston, L., Harthoorn, L. F., van der Beek, E. M., ＆ Workshop, C. I. E. (2011). Obesity in Pregnancy: Implications for the Mother and Lifelong Health of the Child. A Consensus Statement. Pediatric Research, 69(2), 175-180.
Qiu, L., Wu, X., Chau, J. F. L., Szeto, I. Y. Y., Tam, W. Y., Guo, Z., Chung, S. K., Oates, P. J., Chung, S. S. M., ＆ Yang, J. Y. (2008). Aldose Reductase Regulates Hepatic Peroxisome Proliferator-activated Receptor {alpha} Phosphorylation and Activity to Impact Lipid Homeostasis. J. Biol. Chem., 283(25), 17175-17183.
Qiu, L. X., Lin, J. H., Xu, F. G., Gao, Y. H., Zhang, C. L., Liu, Y., Luo, Y., ＆ Yang, J. Y. (2012). Inhibition of Aldose Reductase Activates Hepatic Peroxisome Proliferator-Activated Receptor-alpha and Ameliorates Hepatosteatosis in Diabetic db/db Mice. Experimental Diabetes Research.
Ray, P. D., Huang, B. W., ＆ Tsuji, Y. (2012). Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cellular Signalling, 24(5), 981-990.
Raza, H., Prabu, S. K., John, A., ＆ Avadhani, N. G. (2011). Impaired Mitochondrial Respiratory Functions and Oxidative Stress in Streptozotocin-Induced Diabetic Rats. International Journal of Molecular Sciences, 12(5), 3133-3147.
Ricchi, M., Odoardi, M. R., Carulli, L., Anzivino, C., Ballestri, S., Pinetti, A., Fantoni, L. I., Marra, F., Bertolotti, M., Banni, S., Lonardo, A., Carulli, N., ＆ Loria, P. (2009). Differential effect of oleic and palmitic acid on lipid accumulation and apoptosis in cultured hepatocytes. Journal of Gastroenterology and Hepatology, 24(5), 830-840.
Rocha, H., Ferreira, R., Carvalho, J., Vitorino, R., Santa, C., Lopes, L., Gregersen, N., Vilarinho, L., ＆ Amado, F. (2011). Characterization of mitochondrial proteome in a severe case of ETF-QO deficiency. Journal of Proteomics, 75(1), 221-228.
Rutter, G. A., Xavier, G. D., ＆ Leclerc, I. (2003). Roles of 5 '-AMP-activated protein kinase (AMPK) in mammalian glucose homoeostasis. Biochemical Journal, 375, 1-16.
Schiaffonati, L., Tacchini, L., ＆ Pappalardo, C. (1994). Heat-Shock Response in the Liver - Expression and Regulation of the Hsp70 Gene Family and Early Response Genes after in-Vivo Hyperthermia. Hepatology, 20(4), 975-983.
Senevirathne, M., Jeon, Y. J., Kim, Y. T., Park, P. J., Jung, W. K., Ahn, C. B., ＆ Je, J. Y. (2012). Prevention of oxidative stress in Chang liver cells by gallic acid-grafted-chitosans. Carbohydrate Polymers, 87(1), 876-880.
Singh, S. P. (1976). Levels of Plasma Glycosaminoglycans in Humans with Diabetes-Mellitus. Diabetes, 25, 385-385.
Smith, B. W., ＆ Adams, L. A. (2011). Nonalcoholic fatty liver disease and diabetes mellitus: pathogenesis and treatment. Nature Reviews Endocrinology, 7(8), 456-465.
Song, S., Andrikopoulos, S., Filippis, C., Thorburn, A. W., Khan, D., ＆ Proietto, J. (2001). Mechanism of fat-induced hepatic gluconeogenesis: effect of metformin. American Journal of Physiology - Endocrinology And Metabolism, 281(2), E275-E282.
Song, S., Andrikopoulos, S., Filippis, C., Thorburn, A. W., Khan, D., ＆ Proietto, J. (2001). Mechanism of fat-induced hepatic gluconeogenesis: effect of metformin. Am J Physiol Endocrinol Metab, 281(2), E275-282.
Spamer, C., Heilmann, C., Schiltz, E., Hildebrandt, H., Dietz, C., Gerok, W., ＆ Kreisel, W. (1993). Heat-Shock Protein 60 (Hsp60) of Liver - Identification, Localization and Zonal Pattern. Hepatology, 18(4), A208-A208.
Sunehag, A. L., Bier, D. M., ＆ Haymond, M. W. (2003). High fat diet increases gluconeogenesis in obese but not non-obese adolescents. Pediatric Research, 53(4), 169a-169a.
Tovar, A. R., Diaz-Villasenor, A., Cruz-Salazar, N., Ordaz, G., Granados, O., Palacios-Gonzalez, B., Toyar-Palacio, C., Lopez, P., ＆ Torres, N. (2011). Dietary Type and Amount of Fat Modulate Lipid Metabolism Gene Expression in Liver and in Adipose Tissue in High-fat Diet-fed Rats. Archives of Medical Research, 42(6), 540-553.
van Maldegem, B. T., Duran, M., Wanders, R. J. A., Niezen-Koning, K. E., Hogeveen, M., Ijlst, L., Waterham, H. R., ＆ Wijburg, F. A. (2006). Clinical, biochemical, and genetic heterogeneity in short-chain acyl-coenzyme A dehydrogenase deficiency. Jama-Journal of the American Medical Association, 296(8), 943-952.
Veldhorst, M. A. B., Westerterp-Plantenga, M. S., ＆ Westerterp, K. R. (2009). Gluconeogenesis and energy expenditure after a high-protein, carbohydrate-free diet. American Journal of Clinical Nutrition, 90(3), 519-526.
Vincent, A. M., Hinder, L. M., Pop-Busui, R., ＆ Feldman, E. L. (2009). Hyperlipidemia: a new therapeutic target for diabetic neuropathy. Journal of the Peripheral Nervous System, 14(4), 257-267.
Wang, J. L., Wang, H. G., Hao, P. P., Xue, L., Wei, S. J., Zhang, Y., ＆ Chen, Y. G. (2011). Inhibition of Aldehyde Dehydrogenase 2 by Oxidative Stress Is Associated with Cardiac Dysfunction in Diabetic Rats. Molecular Medicine, 17(3-4), 172-179.
Wang, W. Y., Geng, C. H., Zhang, Y. H., Shi, X., ＆ Ye, J. N. (2007). CE-ED separation and determination of seasonal content variations of some active ingredients in Toona sinensis (A. Juss) Roem leaves. Chromatographia, 66(9-10), 697-701.
Wang, X., Cao, Y. Z., Fu, Y. W., Guo, G. F., ＆ Zhang, X. Y. (2011). Liver fatty acid composition in mice with or without nonalcoholic fatty liver disease. Lipids in Health and Disease, 10.
Weickert, M. O., ＆ Pfeiffer, A. F. H. (2006). Signalling mechanisms linking hepatic glucose and lipid metabolism. Diabetologia, 49(8), 1732-1741.
Yabunaka, N., Ohtsuka, Y., Watanabe, I., Noro, H., Fujisawa, H., ＆ Agishi, Y. (1995). Elevated levels of heat-shock protein 70 (HSP70) in the mononuclear cells of patients with non-insulin-dependent diabetes mellitus. Diabetes Research and Clinical Practice, 30(2), 143-147.
Yamazaki, T., Shiraishi, S., Kishimoto, K., Miura, S., ＆ Ezaki, O. (2011). An increase in liver PPAR gamma 2 is an initial event to induce fatty liver in response to a diet high in butter: PPAR gamma 2 knockdown improves fatty liver induced by high-saturated fat. Journal of Nutritional Biochemistry, 22(6), 543-553.
Yasui, K., Tanabe, H., Miyoshi, N., Suzuki, T., Goto, S., Taguchi, K., Ishigami, Y., Paeng, N., Fukutomi, R., Imai, S., ＆ Isemura, M. (2011). Effects of (-)-epigallocatechin-3-O-gallate on expression of gluconeogenesis-related genes in the mouse duodenum. Biomedical Research-Tokyo, 32(5), 313-320.
Yu, W.-J., Chang, C.-C., Kuo, T.-F., Tsai, T.-C., ＆ Chang, S.-J. (2012). Toona sinensis Roem leaf extracts improve antioxidant activity in the liver of rats under oxidative stress. Food and Chemical Toxicology, 50(6), 1860-1865.
Zhang, D., Xie, L. Y., Jia, G., Cai, S. B., Ji, B. P., Liu, Y. X., Wu, W., Zhou, F., Wang, A. L., Chu, L., Wei, Y., Liu, J., ＆ Gao, F. Y. (2011). Comparative study on antioxidant capacity of flavonoids and their inhibitory effects on oleic acid-induced hepatic steatosis in vitro. European Journal of Medicinal Chemistry, 46(9), 4548-4558.
Zhou, T., Song, Y. C., Feng, M. Q., ＆ Tan, R. X. (2011). Cloning, expression and biochemical characterization of UDP-glucose 6-dehydrogenase, a key enzyme in the biosynthesis of an anti-tumor polysaccharide from the marine fungus Phoma herbarum YS4108. Process Biochemistry, 46(12), 2263-2268.