Expression changes of Akt and GSK-3β during vascular inflammatory response and oxidative stress induced by high-fat diet in rats


Aim: To observe the expression changes of Akt and GSK-3β during vascular inflammatory response and oxidative stress induced by high-fat diet in rats. Methods: 20 male Sprague-Dawley rats were separately fed for 18 weeks with two types of diets; a normal diet (control group, CON) or high-fat diet hyperlipidmia group, HLP). Then the body weight, lipid parameter, plasma hepatocyte growth factor (HGF), serum superoxide dismutase (SOD) , malondialdehyde (MDA), Tumor necrosis factor-α (TNF-α), a Soluble intercellular adhesion molecule-1 (sICAM-1), Lectin-like oxidized cellulose low density lipoprotein receptor-1 (LOX-1), as well as aortic endothelial p-GSK-3β, GSK-3β, p-Akt, Akt expressions were determined. Results: In comparison with the control group, the model group showed a significant increase in the levels of serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol ( LDL-C) and significant decrease in the level of serum high density lipoprotein cholesterol (HDL-C) after high-fat diet for 18 weeks (p < 0.05 or p < 0.01). Meanwhile, a more obvious increase of plasma HGF, LOX-1 and serum MDA, TNF-α, and sICAM-1 levels were observed relative to the control group (p < 0.05 or p < 0.01). Moreover, high-fat diet significantly increased the phosphorylation of Akt and GSK-3β in rat aorta. Conclusion: Short-term high-fat diet could induce vascular endothelium injury by increasing inflammation and oxidative stress. And PI3K/Akt pathway could play an important role in hyperlipidemia-induced vascular endothelium injury.

Share and Cite:

Wang, J. , Yin, H. , Huang, Y. , Guo, C. , Xia, C. and Zhang, L. (2013) Expression changes of Akt and GSK-3β during vascular inflammatory response and oxidative stress induced by high-fat diet in rats. Journal of Biomedical Science and Engineering, 6, 1-5. doi: 10.4236/jbise.2013.65A001.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Malloy M.J. and Kane J.P. (2012) Hyperlipidemia and cardiovascular disease. Current Opinion in Lipidology, 23, 591-592. doi:10.1097/MOL.0b013e328359f162
[2] Ingelsson, E., Massaro, J.M., Sutherland, P., et al. (2009) Contemporary trends in dyslipidemia in the Framingham Heart Study. Archives of Internal Medicine, 169, 279286. doi:10.1001/archinternmed.2008.561
[3] Ross, R. (1999) Atherosclerosisan inflammatory disease. The New England Journal of Medicine, 340, 115-126 doi:10.1056/NEJM199901143400207
[4] Hansson, G.K. (2005) Inflammation, atherosclerosis, and coronary artery disease. The New England Journal of Medicine, 352, 1685-1695. doi:10.1056/NEJMra043430
[5] Stocker, R. and Keaney Jr., J.F. (2004) Role of oxidative modifications in atherosclerosis. Physiological Reviews, 84, 1381-1478. doi:10.1152/physrev.00047.2003
[6] Vanhoutte, P.M. (2009) Endothelial dysfunction: The first step toward coronary arteriosclerosis. Circulation Journal, 73, 595-601. doi:10.1253/circj.CJ-08-1169
[7] Franke, T.F. (2008) PI3K/Akt: Getting it right matters. Oncogene, 27, 6473-6488. doi:10.1038/onc.2008.313
[8] Park, K.W., Yang, H.M., Youn, S.W., et al. (2003) Constitutively active glycogen synthase kinase-3beta gene transfer sustains apoptosis, inhibits proliferation of vascular smooth muscle cells, and reduces neointima formation after balloon injury in rats. Arteriosclerosis, Thrombosis, and Vascular Biology, 23, 1364-1369. doi:10.1161/01.ATV.0000081633.53390.B4
[9] Jenner, A., Ren, M., Rajendran, R., et al. (2007) Zinc supplementation inhibits lipid peroxidation and the development of atherosclerosis in rabbits fed a high cholesterol diet. Free Radical Biology & Medicine, 42, 559566. doi:10.1016/j.freeradbiomed.2006.11.024
[10] Ma, K.L., Ruan, X.Z., Powis, S.H., et al. (2008) Inflammatory stress exacerbates lipid accumulation in hepatic cells and fatty livers of apolipoprotein e knockout mice. Hepatology, 48, 770-781. doi:10.1002/hep.22423
[11] Davis, N.E. (2005) Atherosclerosis—An inflammatory process. Journal of Insurance Medicine, 37, 72-75.
[12] Jiang, W.G. and Hiscox, S. (1997) Hepatocyte growth factor/scatter factor, a cytokine playing multiple and converse roles. Histology and Histopathology, 12, 537-555.
[13] Bonomini, F., Tengattini, S., Fabiano, A., et al. (2008) Atherosclerosis and oxidative stress. Histology and Histopathology, 23, 381-390.
[14] Del Rio, D., Stewart, A.J. and Pellegrini, N. (2005) A review of studies on malondialdehyde as toxic molecule and biological marker of oxidative stress. Nutrition, Metabolism & Cardiovascular Diseases, 15, 316-328. doi:10.1016/j.numecd.2005.05.003
[15] Luo, T. and Xia, Z. (2006) A small dose of hydrogen peroxide enhances tumor necrosis factoralpha toxicity in inducing human vascular endothelial cell apoptosis: Reversal with propofol. Anesthesia & Analgesia, 103, 110116. doi:10.1213/01.ane.0000221183.02244.80
[16] Kleinbongard, P., Heusch, G. and Schulz, R. (2010) TNFalpha in atherosclerosis, myocardial ischemia/reperfusion and heart failure. Pharmacology & Therapeutics, 127, 295-314. doi:10.1016/j.pharmthera.2010.05.002
[17] Frank, P.G. and Lisanti, M.P. (2008) ICAM-1: Role in inflammation and in the regulation of vascular permeability. American Journal of Physiology—Heart and Circulatory Physiology, 295, H926-H927. doi:10.1152/ajpheart.00779.2008
[18] Bourdillon, M.C., Poston, R.N., Covacho, C., et al. (2000) ICAM-1 deficiency reduces atherosclerotic lesions in double-knockout mice (ApoE(-/-)/ICAM-1(-/-)) fed a fat or a chow diet. Arteriosclerosis, Thrombosis, and Vascular Biology, 20, 2630-2635. doi:10.1161/01.ATV.20.12.2630
[19] Mitra, S., Goyal, T. and Mehta, J.L. (2011) Oxidized LDL, LOX-1 and atherosclerosis. Cardiovascular Drugs and Therapy, 25, 419-429. doi:10.1007/s10557-011-6341-5
[20] Girona, J., Manzanares, J.M. and Marimón, F., et al. (2008) Oxidized to non-oxidized lipoprotein ratios are associated with arteriosclerosis and the metabolic syndrome in diabetic patients. Nutrition, Metabolism & Cardiovascular Diseases, 18, 380-387. doi:10.1016/j.numecd.2007.04.002
[21] Chen, M., Masaki, T. and Sawamura, T. (2002) LOX-1, the receptor for oxidized low-density lipoprotein identified from endothelial cells: Implications in endothelial dysfunction and atherosclerosis. Pharmacology & Therapeutics, 95, 89-100. doi:10.1016/S0163-7258(02)00236-X
[22] Riley, J.K., Carayannopoulos, M.O., Wyman, A.H., et al. (2006) Phosphatidylinositol 3-kinase activity is critical for glucose metabolism and embryo survival in murine blastocysts. The Journal of Biological Chemistry, 281, 6010-6019. doi:10.1074/jbc.M506982200.

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.