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標題: 飲食中補充白胺酸對於奧氮平誘發C57BL/6JNarl小鼠肥胖代謝上之影響
Metabolic effects of leucine supplement in olanzapine induced obesity in C57BL/6J Narl mice
作者: 林彥伶
Lin, Yen-Ling
關鍵字: Metabolic syndrome
出版社: 獸醫學系暨研究所
引用: 1. Abraham RT. Identification of TOR signaling complexes: more TORC for the cell growth engine. Cell 2002;111:9-12. 2. Albaugh VL, Vary TC, Ilkayeva O, Wenner BR, Maresca KP, Joyal JL, Breazeale S, Elich TD, Lang CH, Lynch CJ . Atypical Antipsychotics Rapidly and Inappropriately Switch Peripheral Fuel Utilization to Lipids, Impairing Metabolic Flexibility in Rodents. Schizophr Bull 2010. 3. Allison DB, Mentore JL, Heo M, Chandler LP, Cappelleri JC, Infante MC, Weiden PJ. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry 1999;156:1686-1696. 4. Ananth J, Parameswaran S, Gunatilake S. Side effects of atypical antipsychotic drugs. Curr Pharm Des 2004;10:2219-2229. 5. Bhana N, Perry CM. Olanzapine: a review of its use in the treatment of bipolar I disorder. CNS Drugs 2001;15:871-904. 6. Boyda HN, Procyshyn RM, Tse L, Wong D, Pang CC, Honer WG, Barr AM. Intermittent treatment with olanzapine causes sensitization of the metabolic side-effects in rats. Neuropharmacology 2011. 7. Brown EJ, Albers MW, Shin TB, Ichikawa K, Keith CT, Lane WS, Schreiber SL. A mammalian protein targeted by G1-arresting rapamycin-receptor complex. Nature 1994;369:756-758. 8. Chen Q, Reimer RA. Dairy protein and leucine alter GLP-1 release and mRNA of genes involved in intestinal lipid metabolism in vitro. Nutrition 2009;25:340-349. 9. Corradetti MN, Guan KL. Upstream of the mammalian target of rapamycin: do all roads pass through mTOR? Oncogene 2006;25:6347-6360. 10. Donato J, Jr., Pedrosa RG, Cruzat VF, Pires IS, Tirapegui J. Effects of leucine supplementation on the body composition and protein status of rats submitted to food restriction. Nutrition 2006;22:520-527. 11. Farshchi HR, Taylor MA, Macdonald IA. Beneficial metabolic effects of regular meal frequency on dietary thermogenesis, insulin sensitivity, and fasting lipid profiles in healthy obese women. Am J Clin Nutr 2005;81:16-24. 12. Flowers MT, Ntambi JM. Role of stearoyl-coenzyme A desaturase in regulating lipid metabolism. Curr Opin Lipidol 2008;19:248-256. 13. Flowers MT, Ntambi JM. Stearoyl-CoA desaturase and its relation to high-carbohydrate diets and obesity. Biochim Biophys Acta 2009;1791:85-91. 14. Gingras AC, Raught B, Sonenberg N. Regulation of translation initiation by FRAP/mTOR. Genes Dev 2001;15:807-826. 15. Griffin MJ, Sul HS. Insulin regulation of fatty acid synthase gene transcription: roles of USF and SREBP-1c. IUBMB Life 2004;56:595-600. 16. Guo K, Yu YH, Hou J, Zhang Y. Chronic leucine supplementation improves glycemic control in etiologically distinct mouse models of obesity and diabetes mellitus. Nutr Metab (Lond) 2010;7:57. 17. Harris TE, Lawrence JC, Jr. TOR signaling. Sci STKE 2003;2003:re15. 18. Jin H, Meyer JM, Mudaliar S, Jeste DV. Impact of atypical antipsychotic therapy on leptin, ghrelin, and adiponectin. Schizophr Res 2008;100:70-85. 19. Kahn R, Buse J, Ferrannini E, Stern M. The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2005;28:2289-2304. 20. Kim DH, Sabatini DM. Raptor and mTOR: subunits of a nutrient-sensitive complex. Curr Top Microbiol Immunol 2004;279:259-270. 21. Kim DH, Sarbassov DD, Ali SM, King JE, Latek RR, Erdjument-Bromage H, Tempst P, Sabatini DM. mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell 2002;110:163-175. 22. Kim SK, Kim HJ, Ahn CW, Park SW, Cho YW, Lim SK, Lee HC, Cha BS. Hyperleptinemia as a robust risk factor of coronary artery disease and metabolic syndrome in type 2 diabetic patients. Endocr J 2008;55:1085-1092. 23. Kimball SR, Jefferson LS. Regulation of global and specific mRNA translation by oral administration of branched-chain amino acids. Biochem Biophys Res Commun 2004;313:423-427. 24. Knight ZA, Hannan KS, Greenberg ML, Friedman JM. Hyperleptinemia is required for the development of leptin resistance. PLoS One 2010;5:e11376. 25. Layman DK, Walker DA. Potential importance of leucine in treatment of obesity and the metabolic syndrome. J Nutr 2006;136:319S-323S. 26. Llinares Tello F, Hernandez Prats C, Bosacoma Ros N, Perez Martinez E, Climent Grana E, Navarro Polo JN, Ordovas Baines JP. Acute cholestatic hepatitis probably associated with risperidone. Int J Psychiatry Med 2005;35:199-205. 27. Lovegrove JA, Griffin BA. Can dietary modification reduce the cardiovascular complications of metabolic syndrome? ''All for one'' or ''one for all''? Expert Rev Cardiovasc Ther 2011;9:413-416. 28. Lynch CJ, Gern B, Lloyd C, Hutson SM, Eicher R, Vary TC. Leucine in food mediates some of the postprandial rise in plasma leptin concentrations. Am J Physiol Endocrinol Metab 2006;291:E621-630. 29. Mao X, Zeng X, Wang J, Qiao S. Leucine promotes leptin receptor expression in mouse C2C12 myotubes through the mTOR pathway. Mol Biol Rep 2011;38:3201-3206. 30. Marchesini G, Marzocchi R, Agostini F, Bugianesi E. Nonalcoholic fatty liver disease and the metabolic syndrome. Curr Opin Lipidol 2005;16:421-427. 31. Morris DL, Rui L. Recent advances in understanding leptin signaling and leptin resistance. Am J Physiol Endocrinol Metab 2009;297:E1247-1259. 32. Nairizi A, She P, Vary TC, Lynch CJ. Leucine supplementation of drinking water does not alter susceptibility to diet-induced obesity in mice. J Nutr 2009;139:715-719. 33. Newsholme P, Brennan L, Rubi B, Maechler P. New insights into amino acid metabolism, beta-cell function and diabetes. Clin Sci (Lond) 2005;108:185-194. 34. Odaci E, Bilen H, Hacimuftuoglu A, Keles ON, Can I, Bilici M. Long-term treatments with low- and high dose olanzapine change hepatocyte numbers in rats. A stereological and histopathological study. Arch Med Res 2009;40:139-145. 35. Peyrollier K, Hajduch E, Blair AS, Hyde R, Hundal HS. L-leucine availability regulates phosphatidylinositol 3-kinase, p70 S6 kinase and glycogen synthase kinase-3 activity in L6 muscle cells: evidence for the involvement of the mammalian target of rapamycin (mTOR) pathway in the L-leucine-induced up-regulation of system A amino acid transport. Biochem J 2000;350 Pt 2:361-368. 36. Reaven GM. The insulin resistance syndrome: definition and dietary approaches to treatment. Annu Rev Nutr 2005;25:391-406. 37. Renaldi O, Pramono B, Sinorita H, Purnomo LB, Asdie RH, Asdie AH. Hypoadiponectinemia: a risk factor for metabolic syndrome. Acta Med Indones 2009;41:20-24. 38. Roh C, Han J, Tzatsos A, Kandror KV. Nutrient-sensing mTOR-mediated pathway regulates leptin production in isolated rat adipocytes. Am J Physiol Endocrinol Metab 2003;284:E322-330. 39. Ropelle ER, Fernandes MF, Flores MB, Ueno M, Rocco S, Marin R, Cintra DE, Velloso LA, Franchini KG, Saad MJ, Carvalheira JB. Central exercise action increases the AMPK and mTOR response to leptin. PLoS One 2008;3:e3856. 40. Sans MD, Tashiro M, Vogel NL, Kimball SR, D''Alecy LG, Williams JA. Leucine activates pancreatic translational machinery in rats and mice through mTOR independently of CCK and insulin. J Nutr 2006;136:1792-1799. 41. Sarbassov DD, Ali SM, Sengupta S, Sheen JH, Hsu PP, Bagley AF, Markhard AL, Sabatini DM. Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol Cell 2006;22:159-168. 42. Savoy YE, Ashton MA, Miller MW, Nedza FM, Spracklin DK, Hawthorn MH, Rollema H, Matos FF, Hajos-Korcsok E. Differential effects of various typical and atypical antipsychotics on plasma glucose and insulin levels in the mouse: evidence for the involvement of sympathetic regulation. Schizophr Bull 2010;36:410-418. 43. Shah OJ, Anthony JC, Kimball SR, Jefferson LS. 4E-BP1 and S6K1: translational integration sites for nutritional and hormonal information in muscle. Am J Physiol Endocrinol Metab 2000;279:E715-729. 44. She P, Van Horn C, Reid T, Hutson SM, Cooney RN, Lynch CJ. Obesity-related elevations in plasma leucine are associated with alterations in enzymes involved in branched-chain amino acid metabolism. Am J Physiol Endocrinol Metab 2007;293:E1552-1563. 45. Sierra-Johnson J, Unden AL, Linestrand M, Rosell M, Sjogren P, Kolak M, De Faire U, Fisher RM, Hellenius ML. Eating meals irregularly: a novel environmental risk factor for the metabolic syndrome. Obesity (Silver Spring) 2008;16:1302-1307. 46. Steinberger J, Daniels SR, Eckel RH, Hayman L, Lustig RH, McCrindle B, Mietus-Snyder ML. Progress and challenges in metabolic syndrome in children and adolescents: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in the Young Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular Nursing; and Council on Nutrition, Physical Activity, and Metabolism. Circulation 2009;119:628-647. 47. Suryawan A, Jeyapalan AS, Orellana RA, Wilson FA, Nguyen HV, Davis TA. Leucine stimulates protein synthesis in skeletal muscle of neonatal pigs by enhancing mTORC1 activation. Am J Physiol Endocrinol Metab 2008;295:E868-875. 48. Vary TC, Deiter G, Lynch CJ. Rapamycin limits formation of active eukaryotic initiation factor 4F complex following meal feeding in rat hearts. J Nutr 2007;137:1857-1862. 49. Wahba IM, Mak RH. Obesity and obesity-initiated metabolic syndrome: mechanistic links to chronic kidney disease. Clin J Am Soc Nephrol 2007;2:550-562. 50. Wang X, Proud CG. Methods for studying signal-dependent regulation of translation factor activity. Methods Enzymol 2007;431:113-142. 51. Xu G, Kwon G, Cruz WS, Marshall CA, McDaniel ML. Metabolic regulation by leucine of translation initiation through the mTOR-signaling pathway by pancreatic beta-cells. Diabetes 2001;50:353-360. 52. Yoshizawa F, Kimball SR, Vary TC, Jefferson LS. Effect of dietary protein on translation initiation in rat skeletal muscle and liver. Am J Physiol 1998;275:E814-820. 53. Zhang Y, Guo K, LeBlanc RE, Loh D, Schwartz GJ, Yu YH. Increasing dietary leucine intake reduces diet-induced obesity and improves glucose and cholesterol metabolism in mice via multimechanisms. Diabetes 2007;56:1647-1654.
摘要: Metabolic adverse effect is one of the most serious side effects associated with the use of atypical antipsychotics. Some investigators have suggested that some beneficial effects of high protein intake, such as preventing weight gain and promoting loss of body fat, might be attributed to the higher comsumption of branched-chain amino acids (BCAAs), like leucine (Leu). However, it is vague about the anti-obesity effect of leucine in animals treated with antipsychotics. Thus this study investigated the effects of leucine supplement on body weight and lipid metabolism in female C57BL/6JNarl mice treated by olanzapine (Olz). Mice were divided into four groups: olanzapine group (3 mg/kg/day), leucine supplement group (2%water/vol L-leucine), olanzapine combined leucine supplement group and control group. Seven-weeks treatments with olanzapine significantly increased body weight gain and hepatic triglycerides levels that compared to the control group (P < 0.05). However, there was no statistically different for body weight between olanzapine and olanzapine treated with leucine group. Western blotting analysis showed that the expression of FAS and SCD-1 (component of fat synthesis system) were not statistically different among all tested groups. These results suggest that olanzapine exerts some metabolic effects and this leads to increase the accumulation of body weight. However, leucine supplement was not observed to reverse obesity that induced by olanzapine in mice.
其他識別: U0005-2208201113004700
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