Skip to main content
Top
Published in: Cardiovascular Diabetology 1/2012

Open Access 01-12-2012 | Original investigation

Alpha-lipoic acid attenuates cardiac fibrosis in Otsuka Long-Evans Tokushima Fatty rats

Authors: Jung Eun Lee, Chin-ok Yi, Byeong Tak Jeon, Hyun Joo Shin, Soo Kyoung Kim, Tae Sik Jung, Jun Young Choi, Gu Seob Roh

Published in: Cardiovascular Diabetology | Issue 1/2012

Login to get access

Abstract

Background

Hyperglycemia leads to cardiac oxidative stress and an imbalance in glucose homeostasis. Diabetic cardiomyopathy is characterised by cardiac hypertrophy and fibrosis. However, the underlying mechanisms of diabetic cardiomyopathy are not fully understood. This study aimed to investigate the effects of alpha-lipoic acid (ALA) on cardiac energy metabolism, antioxidant effect, and fibrosis in the hearts of Otsuka Long-Evans Tokushima fatty (OLETF) rats.

Methods

Animals were separated into non-diabetic Long-Evans Tokushima Otsuka (LETO) rats and diabetes-prone OLETF rats with or without ALA (200 mg/kg/day) administration for 16 weeks. Diabetic cardiomyopathy was assessed by staining with Sirius Red. The effect of ALA on AMPK signalling, antioxidant enzymes, and fibrosis-related genes in the heart of OLETF rats were performed by Western blot analysis or immunohistochemistry.

Results

Western blot analysis showed that cardiac adenosine monophosphate-activated kinase (AMPK) signalling was lower in OLETF rats than in LETO rats, and that ALA treatment increased the signalling in OLETF rats. Furthermore, the low antioxidant activity in OLETF rats was increased by ALA treatment. In addition to increased Sirius red staining of collagen deposits, transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) were expressed at higher levels in OLETF rat hearts than in LETO rat hearts, and the levels of these factors were decreased by ALA.

Conclusions

ALA enhances AMPK signalling, antioxidant, and antifibrogenic effect. Theses findings suggest that ALA may have beneficial effects in the treatment of diabetic cardiomyopathy.
Appendix
Available only for authorised users
Literature
1.
go back to reference Quiñones-Galvan A, Ferrannini E: Metabolic effects of glucose-insulin infusions: myocardium and whole body. Curr Opin Clin Nutr Metab Care. 2001, 4: 157-163. 10.1097/00075197-200103000-00013.CrossRefPubMed Quiñones-Galvan A, Ferrannini E: Metabolic effects of glucose-insulin infusions: myocardium and whole body. Curr Opin Clin Nutr Metab Care. 2001, 4: 157-163. 10.1097/00075197-200103000-00013.CrossRefPubMed
2.
go back to reference Rodrigues B, McNeill JH: The diabetic heart: metabolic causes for the development of a cardiomyopathy. Cardiovasc Res. 1992, 26: 913-922. 10.1093/cvr/26.10.913.CrossRefPubMed Rodrigues B, McNeill JH: The diabetic heart: metabolic causes for the development of a cardiomyopathy. Cardiovasc Res. 1992, 26: 913-922. 10.1093/cvr/26.10.913.CrossRefPubMed
3.
go back to reference Nunoda S, Genda A, Sugihara N, Nakayama A, Mizuno S, Takeda R: Quantitative approach to the histopathology of the biopsied right ventricular myocardium in patients with diabetes mellitus. Heart Vessels. 1985, 1: 43-47. 10.1007/BF02066486.CrossRefPubMed Nunoda S, Genda A, Sugihara N, Nakayama A, Mizuno S, Takeda R: Quantitative approach to the histopathology of the biopsied right ventricular myocardium in patients with diabetes mellitus. Heart Vessels. 1985, 1: 43-47. 10.1007/BF02066486.CrossRefPubMed
4.
go back to reference Hu E, Liang P, Spiegelman BM: AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem. 1996, 271: 10697-10703. 10.1074/jbc.271.18.10697.CrossRefPubMed Hu E, Liang P, Spiegelman BM: AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem. 1996, 271: 10697-10703. 10.1074/jbc.271.18.10697.CrossRefPubMed
5.
go back to reference Wang X, Hattori Y, Satoh H, Iwata C, Banba N, Monden T, Uchida K, Kamikawa Y, Kasai K: Tetrahydrobiopterin prevents endothelial dysfunction and restores adiponectin levels in rats. Eur J Pharmacol. 2007, 555: 48-53. 10.1016/j.ejphar.2006.10.017.CrossRefPubMed Wang X, Hattori Y, Satoh H, Iwata C, Banba N, Monden T, Uchida K, Kamikawa Y, Kasai K: Tetrahydrobiopterin prevents endothelial dysfunction and restores adiponectin levels in rats. Eur J Pharmacol. 2007, 555: 48-53. 10.1016/j.ejphar.2006.10.017.CrossRefPubMed
6.
go back to reference Guo Z, Xia Z, Yuen VG, McNeill JH: Cardiac expression of adiponectin and its receptors in streptozotocin-induced diabetic rats. Metabolism. 2007, 56: 1363-1371. 10.1016/j.metabol.2007.05.005.CrossRefPubMed Guo Z, Xia Z, Yuen VG, McNeill JH: Cardiac expression of adiponectin and its receptors in streptozotocin-induced diabetic rats. Metabolism. 2007, 56: 1363-1371. 10.1016/j.metabol.2007.05.005.CrossRefPubMed
7.
go back to reference Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, Yamashita S, Noda M, Kita S, Ueki K, Eto K, Akanuma Y, Froguel P, Foufelle F, Ferre P, Carling D, Kimura S, Nagai R, Kahn BB, Kadowaki T: Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med. 2002, 8: 1288-1295. 10.1038/nm788.CrossRefPubMed Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, Yamashita S, Noda M, Kita S, Ueki K, Eto K, Akanuma Y, Froguel P, Foufelle F, Ferre P, Carling D, Kimura S, Nagai R, Kahn BB, Kadowaki T: Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med. 2002, 8: 1288-1295. 10.1038/nm788.CrossRefPubMed
8.
go back to reference Winder WW, Hardie DG: AMP-activated protein kinase, a metabolic master switch: possible roles in type 2 diabetes. Am J Physiol. 1999, 277: E1-E10.PubMed Winder WW, Hardie DG: AMP-activated protein kinase, a metabolic master switch: possible roles in type 2 diabetes. Am J Physiol. 1999, 277: E1-E10.PubMed
9.
go back to reference Shibata R, Ouchi N, Ito M, Kihara S, Shiojima I, Pimentel DR, Kumada M, Sato K, Schiekofer S, Ohashi K, Funahashi T, Colucci WS, Walsh K: Adiponectin-mediated modulation of hypertrophic signals in the heart. Nat Med. 2004, 10: 1384-1389. 10.1038/nm1137.PubMedCentralCrossRefPubMed Shibata R, Ouchi N, Ito M, Kihara S, Shiojima I, Pimentel DR, Kumada M, Sato K, Schiekofer S, Ohashi K, Funahashi T, Colucci WS, Walsh K: Adiponectin-mediated modulation of hypertrophic signals in the heart. Nat Med. 2004, 10: 1384-1389. 10.1038/nm1137.PubMedCentralCrossRefPubMed
11.
go back to reference Henriksen EJ, Diamond-Stanic MK, Marchionne EM: Oxidative stress and the etiology of insulin resistance and type 2 diabetes. Free Radic Biol Med. 2011, 51: 993-999. 10.1016/j.freeradbiomed.2010.12.005.PubMedCentralCrossRefPubMed Henriksen EJ, Diamond-Stanic MK, Marchionne EM: Oxidative stress and the etiology of insulin resistance and type 2 diabetes. Free Radic Biol Med. 2011, 51: 993-999. 10.1016/j.freeradbiomed.2010.12.005.PubMedCentralCrossRefPubMed
12.
go back to reference Bugger H, Abel ED: Rodent models of diabetic cardiomyopathy. Dis Model Mech. 2009, 2: 454-466. 10.1242/dmm.001941.CrossRefPubMed Bugger H, Abel ED: Rodent models of diabetic cardiomyopathy. Dis Model Mech. 2009, 2: 454-466. 10.1242/dmm.001941.CrossRefPubMed
13.
go back to reference Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM: Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys Acta. 2009, 1790: 1149-1160. 10.1016/j.bbagen.2009.07.026.PubMedCentralCrossRefPubMed Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM: Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys Acta. 2009, 1790: 1149-1160. 10.1016/j.bbagen.2009.07.026.PubMedCentralCrossRefPubMed
14.
go back to reference Singh HP, Bowman RH: Effect of DL-alpha-lipoic acid on the citrate concentration and phosphofructokinase activity of perfused hearts from normal and diabetic rats. Biochem Biophys Res Commun. 1970, 41: 555-561. 10.1016/0006-291X(70)90048-3.CrossRefPubMed Singh HP, Bowman RH: Effect of DL-alpha-lipoic acid on the citrate concentration and phosphofructokinase activity of perfused hearts from normal and diabetic rats. Biochem Biophys Res Commun. 1970, 41: 555-561. 10.1016/0006-291X(70)90048-3.CrossRefPubMed
15.
go back to reference Ou P, Tritschler HJ, Wolff SP: Thioctic (lipoic) acid: a therapeutic metal-chelating antioxidant?. Biochem Pharmacol. 1995, 50: 123-126. 10.1016/0006-2952(95)00116-H.CrossRefPubMed Ou P, Tritschler HJ, Wolff SP: Thioctic (lipoic) acid: a therapeutic metal-chelating antioxidant?. Biochem Pharmacol. 1995, 50: 123-126. 10.1016/0006-2952(95)00116-H.CrossRefPubMed
16.
go back to reference Vasdev S, Ford CA, Parai S, Longerich L, Gadag V: Dietary lipoic acid supplementation prevents fructose-induced hypertension in rats. Nutr Metab Cardiovasc Dis. 2000, 10: 339-436.PubMed Vasdev S, Ford CA, Parai S, Longerich L, Gadag V: Dietary lipoic acid supplementation prevents fructose-induced hypertension in rats. Nutr Metab Cardiovasc Dis. 2000, 10: 339-436.PubMed
17.
go back to reference Andrews NC, Faller DV: A rapid micropreparation technique for extraction of DNA-binding proteins from limiting numbers of mammalian cells. Nucleic Acids Res. 1991, 19: 2499-10.1093/nar/19.9.2499.PubMedCentralCrossRefPubMed Andrews NC, Faller DV: A rapid micropreparation technique for extraction of DNA-binding proteins from limiting numbers of mammalian cells. Nucleic Acids Res. 1991, 19: 2499-10.1093/nar/19.9.2499.PubMedCentralCrossRefPubMed
18.
go back to reference Koh EH, Lee WJ, Lee SA, Kim EH, Cho EH, Jeong E, Kim DW, Kim MS, Park JY, Park KG, Lee HJ, Lee IK, Lim S, Jang HC, Lee KH, Lee KU: Effects of alpha-lipoic Acid on body weight in obese subjects. Am J Med. 2011, 124 (85): e1-e8.PubMed Koh EH, Lee WJ, Lee SA, Kim EH, Cho EH, Jeong E, Kim DW, Kim MS, Park JY, Park KG, Lee HJ, Lee IK, Lim S, Jang HC, Lee KH, Lee KU: Effects of alpha-lipoic Acid on body weight in obese subjects. Am J Med. 2011, 124 (85): e1-e8.PubMed
19.
go back to reference Kim MS, Park JY, Namkoong C, Jang PG, Ryu JW, Song HS, Yun JY, Namgoong IS, Ha J, Park IS, Lee IK, Viollet B, Youn JH, Lee HK, Lee KU: Anti-obesity effects of alpha-lipoic acid mediated by suppression of hypothalamic AMP-activated protein kinase. Nat Med. 2004, 10: 727-733. 10.1038/nm1061.CrossRefPubMed Kim MS, Park JY, Namkoong C, Jang PG, Ryu JW, Song HS, Yun JY, Namgoong IS, Ha J, Park IS, Lee IK, Viollet B, Youn JH, Lee HK, Lee KU: Anti-obesity effects of alpha-lipoic acid mediated by suppression of hypothalamic AMP-activated protein kinase. Nat Med. 2004, 10: 727-733. 10.1038/nm1061.CrossRefPubMed
20.
go back to reference Li CJ, Lv L, Li H, Yu DM: Cardiac fibrosis and dysfunction in experimental diabetic cardiomyopathy are ameliorated by alpha-lipoic acid. Cardiovasc Diabetol. 2012, 11: 73-10.1186/1475-2840-11-73.PubMedCentralCrossRefPubMed Li CJ, Lv L, Li H, Yu DM: Cardiac fibrosis and dysfunction in experimental diabetic cardiomyopathy are ameliorated by alpha-lipoic acid. Cardiovasc Diabetol. 2012, 11: 73-10.1186/1475-2840-11-73.PubMedCentralCrossRefPubMed
21.
go back to reference Cremer DR, Rabeler R, Roberts A, Lynch B: Long-term safety of alpha-lipoic acid (ALA) consumption: A 2-year study. Regul Toxicol Pharmacol. 2006, 46: 193-201. 10.1016/j.yrtph.2006.06.003.CrossRefPubMed Cremer DR, Rabeler R, Roberts A, Lynch B: Long-term safety of alpha-lipoic acid (ALA) consumption: A 2-year study. Regul Toxicol Pharmacol. 2006, 46: 193-201. 10.1016/j.yrtph.2006.06.003.CrossRefPubMed
22.
go back to reference Charakida M, Finer N: Drug treatment of obesity in cardiovascular disease. Am J Cardiovasc Drugs. 2012, 12: 93-104. 10.2165/11599000-000000000-00000.CrossRefPubMed Charakida M, Finer N: Drug treatment of obesity in cardiovascular disease. Am J Cardiovasc Drugs. 2012, 12: 93-104. 10.2165/11599000-000000000-00000.CrossRefPubMed
23.
go back to reference Gallagher R, Kirkness A, Armari E, Davidson PM: Weight management issues and strategies for people with high cardiovascular risk undertaking an Australian weight loss program: a focus group study. Nurs Health Sci. 2012, 14: 18-24. 10.1111/j.1442-2018.2011.00651.x.CrossRefPubMed Gallagher R, Kirkness A, Armari E, Davidson PM: Weight management issues and strategies for people with high cardiovascular risk undertaking an Australian weight loss program: a focus group study. Nurs Health Sci. 2012, 14: 18-24. 10.1111/j.1442-2018.2011.00651.x.CrossRefPubMed
24.
go back to reference Wang HT, Liu CF, Tsai TH, Chen YL, Chang HW, Tsai CY, Leu S, Zhen YY, Chai HT, Chung SY, Chua S, Yen CH, Yip HK: Effect of obesity reduction on preservation of heart function and attenuation of left ventricular remodeling, oxidative stress and inflammation in obese mice. J Transl Med. 2012, 10: 145-10.1186/1479-5876-10-145.PubMedCentralCrossRefPubMed Wang HT, Liu CF, Tsai TH, Chen YL, Chang HW, Tsai CY, Leu S, Zhen YY, Chai HT, Chung SY, Chua S, Yen CH, Yip HK: Effect of obesity reduction on preservation of heart function and attenuation of left ventricular remodeling, oxidative stress and inflammation in obese mice. J Transl Med. 2012, 10: 145-10.1186/1479-5876-10-145.PubMedCentralCrossRefPubMed
25.
go back to reference Díez JJ, Iglesias P: The role of the novel adipocyte-derived hormone adiponectin in human disease. Eur J Endocrinol. 2003, 148: 293-300. 10.1530/eje.0.1480293.CrossRefPubMed Díez JJ, Iglesias P: The role of the novel adipocyte-derived hormone adiponectin in human disease. Eur J Endocrinol. 2003, 148: 293-300. 10.1530/eje.0.1480293.CrossRefPubMed
26.
go back to reference Park SY, Cho YR, Kim HJ, Higashimori T, Danton C, Lee MK, Dey A, Rothermel B, Kim YB, Kalinowski A, Russell KS, Kim JK: Unraveling the temporal pattern of diet-induced insulin resistance in individual organs and cardiac dysfunction in C57BL/6 mice. Diabetes. 2005, 54: 3530-3540. 10.2337/diabetes.54.12.3530.CrossRefPubMed Park SY, Cho YR, Kim HJ, Higashimori T, Danton C, Lee MK, Dey A, Rothermel B, Kim YB, Kalinowski A, Russell KS, Kim JK: Unraveling the temporal pattern of diet-induced insulin resistance in individual organs and cardiac dysfunction in C57BL/6 mice. Diabetes. 2005, 54: 3530-3540. 10.2337/diabetes.54.12.3530.CrossRefPubMed
27.
go back to reference Jung TS, Kim SK, Shin HJ, Jeon BT, Hahm JR, Roh GS: α-lipoic acid prevents nonalcoholic fatty liver disease in OLETF rats. Liver Int. 2012, 32: 1565-1573. 10.1111/j.1478-3231.2012.02857.x.CrossRefPubMed Jung TS, Kim SK, Shin HJ, Jeon BT, Hahm JR, Roh GS: α-lipoic acid prevents nonalcoholic fatty liver disease in OLETF rats. Liver Int. 2012, 32: 1565-1573. 10.1111/j.1478-3231.2012.02857.x.CrossRefPubMed
28.
go back to reference Yamada E, Lee TW, Pessin JE, Bastie CC: Targeted therapies of the LKB1/AMPK pathway for the treatment of insulin resistance. Future Med Chem. 2010, 2: 1785-1796. 10.4155/fmc.10.264.PubMedCentralCrossRefPubMed Yamada E, Lee TW, Pessin JE, Bastie CC: Targeted therapies of the LKB1/AMPK pathway for the treatment of insulin resistance. Future Med Chem. 2010, 2: 1785-1796. 10.4155/fmc.10.264.PubMedCentralCrossRefPubMed
29.
go back to reference Sriwijitkamol A, Ivy JL, Christ-Roberts C, DeFronzo RA, Mandarino LJ, Musi N: LKB1-AMPK signaling in muscle from obese insulin-resistant Zucker rats and effects of training. Am J Physiol Endocrinol Metab. 2006, 290: E925-E932. 10.1152/ajpendo.00429.2005.CrossRefPubMed Sriwijitkamol A, Ivy JL, Christ-Roberts C, DeFronzo RA, Mandarino LJ, Musi N: LKB1-AMPK signaling in muscle from obese insulin-resistant Zucker rats and effects of training. Am J Physiol Endocrinol Metab. 2006, 290: E925-E932. 10.1152/ajpendo.00429.2005.CrossRefPubMed
30.
go back to reference Lee Y, Naseem RH, Park BH, Garry DJ, Richardson JA, Schaffer JE, Unger RH: Alpha-lipoic acid prevents lipotoxic cardiomyopathy in acyl CoA-synthase transgenic mice. Biochem Biophys Res Commun. 2006, 344: 446-452. 10.1016/j.bbrc.2006.03.062.CrossRefPubMed Lee Y, Naseem RH, Park BH, Garry DJ, Richardson JA, Schaffer JE, Unger RH: Alpha-lipoic acid prevents lipotoxic cardiomyopathy in acyl CoA-synthase transgenic mice. Biochem Biophys Res Commun. 2006, 344: 446-452. 10.1016/j.bbrc.2006.03.062.CrossRefPubMed
31.
go back to reference Chen WL, Kang CH, Wang SG, Lee HM: α-Lipoic acid regulates lipid metabolism through induction of sirtuin 1 (SIRT1) and activation of AMP-activated protein kinase. Diabetologia. 2012, 55: 1824-1835. 10.1007/s00125-012-2530-4.CrossRefPubMed Chen WL, Kang CH, Wang SG, Lee HM: α-Lipoic acid regulates lipid metabolism through induction of sirtuin 1 (SIRT1) and activation of AMP-activated protein kinase. Diabetologia. 2012, 55: 1824-1835. 10.1007/s00125-012-2530-4.CrossRefPubMed
32.
go back to reference Eberlé D, Hegarty B, Bossard P, Ferré P, Foufelle F: SREBP transcription factors: master regulators of lipid homeostasis. Biochimie. 2004, 86: 839-848. 10.1016/j.biochi.2004.09.018.CrossRefPubMed Eberlé D, Hegarty B, Bossard P, Ferré P, Foufelle F: SREBP transcription factors: master regulators of lipid homeostasis. Biochimie. 2004, 86: 839-848. 10.1016/j.biochi.2004.09.018.CrossRefPubMed
33.
go back to reference Guo Z, Zheng C, Qin Z, Wei P: Effect of telmisartan on the expression of cardiac adiponectin and its receptor 1 in type 2 diabetic rats. J Pharm Pharmacol. 2011, 63: 87-94. 10.1111/j.2042-7158.2010.01157.x.CrossRefPubMed Guo Z, Zheng C, Qin Z, Wei P: Effect of telmisartan on the expression of cardiac adiponectin and its receptor 1 in type 2 diabetic rats. J Pharm Pharmacol. 2011, 63: 87-94. 10.1111/j.2042-7158.2010.01157.x.CrossRefPubMed
34.
go back to reference Kohjima M, Higuchi N, Kato M, Kotoh K, Yoshimoto T, Fujino T, Yada M, Yada R, Harada N, Enjoji M, Takayanagi R, Nakamuta M: SREBP-1c, regulated by the insulin and AMPK signaling pathways, plays a role in nonalcoholic fatty liver disease. Int J Mol Med. 2008, 21: 507-511.PubMed Kohjima M, Higuchi N, Kato M, Kotoh K, Yoshimoto T, Fujino T, Yada M, Yada R, Harada N, Enjoji M, Takayanagi R, Nakamuta M: SREBP-1c, regulated by the insulin and AMPK signaling pathways, plays a role in nonalcoholic fatty liver disease. Int J Mol Med. 2008, 21: 507-511.PubMed
35.
go back to reference Song KH, Lee WJ, Koh JM, Kim HS, Youn JY, Park HS, Koh EH, Kim MS, Youn JH, Lee KU, Park JY: Alpha-Lipoic acid prevents diabetes mellitus in diabetes-prone obese rats. Biochem Biophys Res Commun. 2005, 326: 197-202.CrossRefPubMed Song KH, Lee WJ, Koh JM, Kim HS, Youn JY, Park HS, Koh EH, Kim MS, Youn JH, Lee KU, Park JY: Alpha-Lipoic acid prevents diabetes mellitus in diabetes-prone obese rats. Biochem Biophys Res Commun. 2005, 326: 197-202.CrossRefPubMed
36.
go back to reference Hao J, Zhu L, Zhao S, Liu S, Liu Q, Duan H: PTEN ameliorates high glucose-induced lipid deposits through regulating SREBP-1/FASN/ACC pathway in renal proximal tubular cells. Exp Cell Res. 2011, 317: 1629-1639. 10.1016/j.yexcr.2011.02.003.CrossRefPubMed Hao J, Zhu L, Zhao S, Liu S, Liu Q, Duan H: PTEN ameliorates high glucose-induced lipid deposits through regulating SREBP-1/FASN/ACC pathway in renal proximal tubular cells. Exp Cell Res. 2011, 317: 1629-1639. 10.1016/j.yexcr.2011.02.003.CrossRefPubMed
37.
go back to reference Abel ED, Kaulbach HC, Tian R, Hopkins JC, Duffy J, Doetschman T, Minnemann T, Boers ME, Hadro E, Oberste-Berghaus C, Quist W, Lowell BB, Ingwall JS, Kahn BB: Cardiac hypertrophy with preserved contractile function after selective deletion of GLUT4 from the heart. J Clin Invest. 1999, 104: 1703-1714. 10.1172/JCI7605.PubMedCentralCrossRefPubMed Abel ED, Kaulbach HC, Tian R, Hopkins JC, Duffy J, Doetschman T, Minnemann T, Boers ME, Hadro E, Oberste-Berghaus C, Quist W, Lowell BB, Ingwall JS, Kahn BB: Cardiac hypertrophy with preserved contractile function after selective deletion of GLUT4 from the heart. J Clin Invest. 1999, 104: 1703-1714. 10.1172/JCI7605.PubMedCentralCrossRefPubMed
38.
go back to reference Park SY, Choi GH, Choi HI, Ryu J, Jung CY, Lee W: Calorie restriction improves whole-body glucose disposal and insulin resistance in association with the increased adipocyte-specific GLUT4 expression in Otsuka Long-Evans Tokushima fatty rats. Arch Biochem Biophys. 2005, 436: 276-284. 10.1016/j.abb.2005.01.010.CrossRefPubMed Park SY, Choi GH, Choi HI, Ryu J, Jung CY, Lee W: Calorie restriction improves whole-body glucose disposal and insulin resistance in association with the increased adipocyte-specific GLUT4 expression in Otsuka Long-Evans Tokushima fatty rats. Arch Biochem Biophys. 2005, 436: 276-284. 10.1016/j.abb.2005.01.010.CrossRefPubMed
39.
go back to reference Nishiumi S, Ashida H: Rapid preparation of a plasma membrane fraction from adipocytes and muscle cells: application to detection of translocated glucose transporter 4 on the plasma membrane. Biosci Biotechnol Biochem. 2007, 71: 2343-2346. 10.1271/bbb.70342.CrossRefPubMed Nishiumi S, Ashida H: Rapid preparation of a plasma membrane fraction from adipocytes and muscle cells: application to detection of translocated glucose transporter 4 on the plasma membrane. Biosci Biotechnol Biochem. 2007, 71: 2343-2346. 10.1271/bbb.70342.CrossRefPubMed
40.
go back to reference Penumathsa SV, Thirunavukkarasu M, Zhan L, Maulik G, Menon VP, Bagchi D, Maulik N: Resveratrol enhances GLUT-4 translocation to the caveolar lipid raft fractions through AMPK/Akt/eNOS signalling pathway in diabetic myocardium. J Cell Mol Med. 2008, 12: 2350-2361. 10.1111/j.1582-4934.2008.00251.x.PubMedCentralCrossRefPubMed Penumathsa SV, Thirunavukkarasu M, Zhan L, Maulik G, Menon VP, Bagchi D, Maulik N: Resveratrol enhances GLUT-4 translocation to the caveolar lipid raft fractions through AMPK/Akt/eNOS signalling pathway in diabetic myocardium. J Cell Mol Med. 2008, 12: 2350-2361. 10.1111/j.1582-4934.2008.00251.x.PubMedCentralCrossRefPubMed
41.
go back to reference Barlovic DP, Soro-Paavonen A, Jandeleit-Dahm KA: RAGE biology, atherosclerosis and diabetes. Clin Sci (Lond). 2011, 121: 43-55. 10.1042/CS20100501.CrossRef Barlovic DP, Soro-Paavonen A, Jandeleit-Dahm KA: RAGE biology, atherosclerosis and diabetes. Clin Sci (Lond). 2011, 121: 43-55. 10.1042/CS20100501.CrossRef
42.
go back to reference Kuhla A, Hettwer C, Menger MD, Vollmar B: Oxidative stress-associated rise of hepatic protein glycation increases inflammatory liver injury in uncoupling protein-2 deficient mice. Lab Invest. 2010, 90: 1189-1198. 10.1038/labinvest.2010.84.CrossRefPubMed Kuhla A, Hettwer C, Menger MD, Vollmar B: Oxidative stress-associated rise of hepatic protein glycation increases inflammatory liver injury in uncoupling protein-2 deficient mice. Lab Invest. 2010, 90: 1189-1198. 10.1038/labinvest.2010.84.CrossRefPubMed
43.
go back to reference Ogborne RM, Rushworth SA, O'Connell MA: Alpha-lipoic acid-induced heme oxygenase-1 expression is mediated by nuclear factor erythroid 2-related factor 2 and p38 mitogen-activated protein kinase in human monocytic cells. Arterioscler Thromb Vasc Biol. 2005, 25: 2100-2105. 10.1161/01.ATV.0000183745.37161.6e.CrossRefPubMed Ogborne RM, Rushworth SA, O'Connell MA: Alpha-lipoic acid-induced heme oxygenase-1 expression is mediated by nuclear factor erythroid 2-related factor 2 and p38 mitogen-activated protein kinase in human monocytic cells. Arterioscler Thromb Vasc Biol. 2005, 25: 2100-2105. 10.1161/01.ATV.0000183745.37161.6e.CrossRefPubMed
44.
go back to reference Nicolai A, Li M, Kim DH, Peterson SJ, Vanella L, Positano V, Gastaldelli A, Rezzani R, Rodella LF, Drummond G, Kusmic C, L'Abbate A, Kappas A, Abraham NG: Heme oxygenase-1 induction remodels adipose tissue and improves insulin sensitivity in obesity-induced diabetic rats. Hypertension. 2009, 53: 508-515. 10.1161/HYPERTENSIONAHA.108.124701.PubMedCentralCrossRefPubMed Nicolai A, Li M, Kim DH, Peterson SJ, Vanella L, Positano V, Gastaldelli A, Rezzani R, Rodella LF, Drummond G, Kusmic C, L'Abbate A, Kappas A, Abraham NG: Heme oxygenase-1 induction remodels adipose tissue and improves insulin sensitivity in obesity-induced diabetic rats. Hypertension. 2009, 53: 508-515. 10.1161/HYPERTENSIONAHA.108.124701.PubMedCentralCrossRefPubMed
45.
go back to reference Cai L, Kang YJ: Cell death and diabetic cardiomyopathy. Cardiovasc Toxicol. 2003, 3: 219-228. 10.1385/CT:3:3:219.CrossRefPubMed Cai L, Kang YJ: Cell death and diabetic cardiomyopathy. Cardiovasc Toxicol. 2003, 3: 219-228. 10.1385/CT:3:3:219.CrossRefPubMed
46.
go back to reference Li X, Xu Z, Li S, Rozanski GJ: Redox regulation of Ito remodeling in diabetic rat heart. Am J Physiol Heart Circ Physiol. 2005, 288: H1417-H1424.CrossRefPubMed Li X, Xu Z, Li S, Rozanski GJ: Redox regulation of Ito remodeling in diabetic rat heart. Am J Physiol Heart Circ Physiol. 2005, 288: H1417-H1424.CrossRefPubMed
47.
go back to reference Lim YH, Joe JH, Jang KS, Song YS, So BI, Fang CH, Shin J, Kim JH, Lim HK, Kim KS: Effects of granulocyte-colony stimulating factor (G-CSF) on diabetic cardiomyopathy in Otsuka Long-Evans Tokushima fatty rats. Cardiovasc Diabetol. 2011, 10: 92-10.1186/1475-2840-10-92.PubMedCentralCrossRefPubMed Lim YH, Joe JH, Jang KS, Song YS, So BI, Fang CH, Shin J, Kim JH, Lim HK, Kim KS: Effects of granulocyte-colony stimulating factor (G-CSF) on diabetic cardiomyopathy in Otsuka Long-Evans Tokushima fatty rats. Cardiovasc Diabetol. 2011, 10: 92-10.1186/1475-2840-10-92.PubMedCentralCrossRefPubMed
48.
go back to reference Shimizu M, Umeda K, Sugihara N, Yoshio H, Ino H, Takeda R, Okada Y, Nakanishi I: Collagen remodelling in myocardia of patients with diabetes. J Clin Pathol. 1993, 46: 32-36. 10.1136/jcp.46.1.32.PubMedCentralCrossRefPubMed Shimizu M, Umeda K, Sugihara N, Yoshio H, Ino H, Takeda R, Okada Y, Nakanishi I: Collagen remodelling in myocardia of patients with diabetes. J Clin Pathol. 1993, 46: 32-36. 10.1136/jcp.46.1.32.PubMedCentralCrossRefPubMed
49.
go back to reference Brand T, Schneider MD: The TGF beta superfamily in myocardium: ligands, receptors, transduction, and function. J Mol Cell Cardiol. 1995, 27: 5-18. 10.1016/S0022-2828(08)80003-X.CrossRefPubMed Brand T, Schneider MD: The TGF beta superfamily in myocardium: ligands, receptors, transduction, and function. J Mol Cell Cardiol. 1995, 27: 5-18. 10.1016/S0022-2828(08)80003-X.CrossRefPubMed
50.
go back to reference Pathak M, Sarkar S, Vellaichamy E, Sen S: Role of myocytes in myocardial collagen production. Hypertension. 2001, 37: 833-840. 10.1161/01.HYP.37.3.833.CrossRefPubMed Pathak M, Sarkar S, Vellaichamy E, Sen S: Role of myocytes in myocardial collagen production. Hypertension. 2001, 37: 833-840. 10.1161/01.HYP.37.3.833.CrossRefPubMed
51.
go back to reference Watanabe K, Thandavarayan RA, Harima M, Sari FR, Gurusamy N, Veeraveedu PT, Mito S, Arozal W, Sukumaran V, Laksmanan AP, Soetikno V, Kodama M, Aizawa Y: Role of differential signaling pathways and oxidative stress in diabetic cardiomyopathy. Curr Cardiol Rev. 2010, 6: 280-290. 10.2174/157340310793566145.PubMedCentralCrossRefPubMed Watanabe K, Thandavarayan RA, Harima M, Sari FR, Gurusamy N, Veeraveedu PT, Mito S, Arozal W, Sukumaran V, Laksmanan AP, Soetikno V, Kodama M, Aizawa Y: Role of differential signaling pathways and oxidative stress in diabetic cardiomyopathy. Curr Cardiol Rev. 2010, 6: 280-290. 10.2174/157340310793566145.PubMedCentralCrossRefPubMed
Metadata
Title
Alpha-lipoic acid attenuates cardiac fibrosis in Otsuka Long-Evans Tokushima Fatty rats
Authors
Jung Eun Lee
Chin-ok Yi
Byeong Tak Jeon
Hyun Joo Shin
Soo Kyoung Kim
Tae Sik Jung
Jun Young Choi
Gu Seob Roh
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2012
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/1475-2840-11-111

Other articles of this Issue 1/2012

Cardiovascular Diabetology 1/2012 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.