DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20181170

Effect of Lutein in the expression of PPARα and LDLR in hypercholesterolemic male Wistar Rats

Soundarya Priyadharsini K., Nirmala P., Ashok Kumar P., Krishna Prasad T.

Abstract


Background: Hyperlipidemia is a well known risk factor for cardiovascular disease, especially atherosclerotic coronary artery disease. Peroxisome proliferator activated receptor α (PPARα), a member of this nuclear receptor family, has emerged as an important player in this scenario, with evidence supporting a central co-ordinated role in the regulation of fatty acid oxidation, lipid and lipoprotein metabolism and inflammatory and vascular responses, all of which would be predicted to reduce atherosclerotic risk. The low-density lipoprotein (LDL) receptor (LDLR) is the primary pathway for removal of cholesterol from the circulation, and its activity is meticulously governed by intracellular cholesterol levels. Hence in this study we investigated the effect of Lutein on PPARα and LDLR expression in liver of wistar rats.

Methods: Male Wistar rats were divided into 6 groups of 6 each. Group I served as control. Group II III, IV, V and VI rats were received high cholesterol diet. Group III was treated with Atorvastatin 5mg/kg. Group IV, V and VI rats were treated with 25mg/kg, 50mg/kg and 100mg/kg of Lutein. After 16 weeks, liver tissue samples were collected from all the groups of animals to evaluate the expression of PPARα and LDLR.

Results: The expression of Peroxisome proliferator activated receptor α and low-density lipoprotein (LDL) receptor (LDLR) was significantly increased in Lutein treated hypercholesterolemic male wistar rats.

Conclusions: The results of this study indicate that Lutein activates LDL receptor and PPARα in hypercholesterolemic male wistar rats.


Keywords


Hypercholesterolemia, LDL receptor, Liver, Lutein, PPARα

Full Text:

PDF

References


Fruchart JC. Peroxisome proliferator-activated receptor-alpha (PPARalpha): at the crossroads of obesity, diabetes and cardiovascular disease. Atherosclerosis. 2009 Jul;205(1):1-8. Epub 2009 Mar 20.

Ravnskjaer K, Frigerio F, Boergesen M, Nielsen T, Maechler P, Mandrup S. PPARδ is a fatty acid sensor that enhances mitochondrial oxidation in insulin-secreting cells and protects against fatty acid-induced dysfunction. Journal of Lipid Research. 2010;51.

I.Issemann, Green S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature. 1990;347(6294):645-50.

Desvergne B, Wahli W. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocrine Reviews. 1999;20(5):649-88.

Barbier O, Torra IP, Duguay Y, Blanquart C, Fruchart JC, Glineur C, Staels B. Pleiotropic actions of peroxisome proliferator–activated receptors in lipid metabolism and atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology. 2002 May 1;22(5):717-26.

Chinetti-Gbaguidi G, Fruchart JC, Staels B. Role of the PPAR family of nuclear receptors in the regulation of metabolic and cardiovascular homeostasis: new approaches to therapy. Curr Opin Pharmacol 2005;5:177-83.

IJpenberg A, Jeannin E, Wahli W, Desvergne B. Polarity and specific sequence requirements of peroxisome proliferator-activated receptor (PPAR)/retinoid X receptor heterodimer binding to DNA. A functional analysis of the malic enzyme gene PPAR response element. J Biol Chem. 1997;272:20108-17.

Feige JN, Gelman L, Michalik L, Desvergne B, Wahli W. From molecular action to physiological outputs: peroxisome proliferator-activated receptors are nuclear receptors at the crossroads of key cellular functions. Prog Lipid Res. 2006;45(2):120-59.

Martin G, Schoonjans K, Lefebvre AM, Staels B, Auwerx J. Coordinate regulation of the expression of the fatty acid transport protein and acyl-CoA synthetase genes by PPARalpha and PPARgamma activators. J Biol Chem. 1997;272:28210-7.

Chinetti-Gbaguidi G, Fruchart JC, Staels B. Role of the PPAR family of nuclear receptors in the regulation of metabolic and cardiovascular homeostasis: new approaches to therapy. Curr Opin Pharmacol. 2005;5:177-83.

Prieur X, Coste H, Rodriguez JC. The human apolipoprotein AV gene is regulated by PPAR and contains a novel FXR response element. J Biol Chem. 2003;278:25468-80.

Raspé E, Duez H, Mansén A, Fontaine C, Fiévet C, Fruchart JC, et al. Identification of Rev-erbα as a physiological repressor of apoC-III gene transcription. Journal of lipid research. 2002 Dec 1;43(12):2172-9.

Hiukka A, Fruchart-Najib J, Leinonen E, Hilden H, Fruchart JC, Taskinen MR. Alterations of lipids and apolipoprotein CIII in very low density lipoprotein subspecies in type 2 diabetes. Diabetologia. 2005 Jun 1;48(6):1207-15.

Chinetti G, Lestavel S, Remaley A, Neve B, Torra IP, Minnich A, Jaye M, Duverger N, Brewer HB, Fruchart JC, Clavey V. PPAR alpha and PPAR gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABC-1 pathway. Circulation. 2000 Oct 31;102(18):311.

Chinetti G, Lestavel S, Fruchart JC, Clavey V, Staels B. Peroxisome proliferator-activated receptor α reduces cholesterol esterification in macrophages. Circulation research. 2003 Feb 7;92(2):212-7.

Chinetti-Gbaguidi G, Rigamonti E, Helin L, Mutka AL, Lepore M, Fruchart JC, et al. Peroxisome proliferator-activated receptor α controls cellular cholesterol trafficking in macrophages. Journal of lipid research. 2005 Dec 1;46(12):2717-25.

Staels B, Koenig W, Habib A, Merval R, Lebret M, Torra IP, et al. Activation of human aortic smooth-muscle cells is inhibited by PPARα but not by PPARγ activators. Nature. 1998 Jun;393(6687):790.

Delerive P, Martin-Nizard F, Chinetti G, Trottein F, Fruchart JC, Najib J, et al. Peroxisome proliferator-activated receptor activators inhibit thrombin-induced endothelin-1 production in human vascular endothelial cells by inhibiting the activator protein-1 signaling pathway. Circulation research. 1999 Sep 3;85(5):394-402.

Slater HR, McKinney L, Packard CJ, Shepherd J. Contribution of the receptor pathway to low density lipoprotein catabolism in humans. New methods for quantitation. Arteriosclerosis, Thrombosis, and Vascular Biology. 1984 Nov 1;4(6):604-13.

Goldstein JL, Brown MS. The LDL receptor. Arteriosclerosis, thrombosis, and vascular biology. 2009 Apr 1;29(4):431-8.

Hobbs HH, Brown MS, Goldstein JL. Molecular genetics of the LDL receptor gene in familial hypercholesterolemia. Human mutation. 1992 Jan 1;1(6):445-66.

Soutar AK. LDL Receptor and Its Role in Inherited Disease. Medical Research Council Clinical Sciences; September 2010.

Soutar AK, Naoumova RP. Mechanisms of disease: genetic causes of familial hypercholesterolemia. Nature Reviews Cardiology. 2007 Apr;4(4):214.

Austin A, Elsie CS, Thirugnanasambantham P. Evaluating the clinical efficacy of a polyherbal formulation Arogh plus on stress a randomised clinical study. Journal of Stress Physiology & Biochemistry. 2011;7(1).

Hao H, Wei C, Danhong G, Bingquing H, Lin F. Oxygenated carotenoid Lutein supplementation against early atherosclerosis in apo-deficient mice through alleviation the dyslipidemia and attenuation the oxidative stress.

Sher T, Yi HF, McBride OW, Gonzalez FJ. cDNA cloning, chromosomal mapping, and functional characterization of human peroxisome proliferator activated receptor. Biochemistry. 1993;32(21):5598-604.

Kersten S, Seydoux J, Peters JM, Gonzalez FJ, Desvergne B, Wahli W. Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting; J Clin Invest. 1999;103(11):1489-98.

Kersten S. Integrated physiology and systems biology of PPARα. Molecular metabolism. 2014;3:354-71. PMC 4060217, PMID 24944896.

Braissant O, Foufelle F, Scotto C, Dauca M, Wahli W. Differential expression of peroxisome proliferator-activated receptors (PPARs) tissue distribution of PPAR-α, β, and γ in the adult rat. Endocrinology. 1995;137(1):354-66.

Sheng L, Ye P, Liu YX. Atorvastatin upregulates the expression of PPAR alpha/gamma and inhibits the hypertrophy of cardiac myocytes in vitro; Zhonghua Xin Xue Guan Bing Za Zhi. 2005;33(12)1080-4.

Pocathikorn A, Taylor RR, Mamotte CD. Atorvastatin increases expression of low-density lipoprotein receptor mRNA in human circulating mononuclear cells; Clin. Exp. Pharmacol. Physiol. 2010;37(4):471-6.