Generic placeholder image

Current Functional Foods

Editor-in-Chief

ISSN (Print): 2666-8629
ISSN (Online): 2666-8637

Research Article

Curcumin Modulates the Expression of PPARα, CPT1, and MCAD to Prevent Lipid Metabolism Alterations in the Hearts of Mice Fed with an HFD

Author(s): Cecilia G. Meléndez-Salcido, Katya Vargas-Ortiz, Oscar G. Silva-Gaona, María C. León-García, Maciste H. Macías-Cervantes, Joel Ramírez-Emiliano and Victoriano Pérez-Vázquez*

Volume 1, Issue 1, 2023

Published on: 23 August, 2022

Article ID: e260422204055 Pages: 7

DOI: 10.2174/2666862901666220426103916

Abstract

Background: Consuming a high-fructose diet (HFD) contributes to obesity, dyslipidemia, and cardiovascular diseases. It has been proposed that curcumin modulates lipid metabolism, and it has a potential beneficial effect in the context of cardiometabolic diseases, although it has not been demonstrated.

Objective: This article evaluates the effect of curcumin on the expression of the PPARα, CPT1, MCAD, VLCAD, and ACAA2 genes in the hearts of mice fed with an HFD.

Methods: Four groups of male C57BL/6 mice (n = 6) were treated for 15 weeks as follows: 1) standard diet (C), 2) standard diet + 0.75% (w/w) curcumin (C+Cur), 3) standard diet + 30% (w/v) fructose (F), and 4) standard diet + 0.75% (w/w) curcumin + 30% (w/v) fructose (F+Cur). Bodyweight gain, glucose, and the overall serum cholesterol levels were measured after the treatment. The expression of PPARα, MCAD, VLCAD, ACAA2, and CPT1 was assessed by Western blot in mice hearts.

Results: Our data showed that a curcumin treatment induced a higher expression of PPARα and ACAA2, whereas it decreased CPT1 and MCAD expression in the hearts of mice fed with an HFD. However, it did not affect VLCAD expression.

Conclusion: Curcumin regulated PPARα, CPT1, and MCAD expression and increased that of ACAA2. This suggests a possible therapeutic use to prevent the alterations of mitochondrial fatty acid metabolism in the hearts of mice fed with an HFD.

Keywords: Cardiovascular disease, curcuma longa, high-fructose diet, lipid metabolism, mitochondrial metabolism, obesity.

Graphical Abstract
[1]
Taskinen MR, Packard CJ, Borén J. Dietary fructose and the metabolic syndrome. Nutrients 2019; 11(9): 1987.
[2]
Ter Horst KW, Serlie MJ. Fructose consumption, lipogenesis, and non-alcoholic fatty liver disease. Nutrients 2017; 9(9): 981.
[3]
Zhang DM, Jiao RQ, Kong LD. High dietary fructose: Direct or indirect dangerous factors disturbing tissue and organ functions. Nutrients 2017; 9(4): 335.
[4]
Jaswal JS, Keung W, Wang W, Ussher JR, Lopaschuk GD. Targeting fatty acid and carbohydrate oxidation - A novel therapeutic intervention in the ischemic and failing heart. Biochim Biophys Acta 2011; 1813(7): 1333-50.
[http://dx.doi.org/10.1016/j.bbamcr.2011.01.015] [PMID: 21256164]
[5]
Han L, Liu J, Zhu L, et al. Free fatty acid can induce cardiac dysfunction and alter insulin signaling pathways in the heart. Lipids Health Dis 2018; 17: 185.
[6]
Grygiel-Górniak B. Peroxisome proliferator-activated receptors and their ligands: Nutritional and clinical implications--a review. Nutr J 2014; 13: 17.
[http://dx.doi.org/10.1186/1475-2891-13-17] [PMID: 24524207]
[7]
Neels JG, Grimaldi PA. Physiological functions of peroxisome proliferator-activated receptor β. Physiol Rev 2014; 94(3): 795-858.
[8]
Fillmore N, Lopaschuk GD. Malonyl CoA: A promising target for the treatment of cardiac disease. IUBMB Life 2014; 66: 139-46.
[http://dx.doi.org/10.1002/iub.1253]
[9]
Fillmore N, Mori J, Lopaschuk GD. Mitochondrial fatty acid oxidation alterations in heart failure, ischaemic heart disease and diabetic cardiomyopathy. Br J Pharmacol 2014; 2080-90.
[10]
Yang Y, Feng Y, Zhang X, et al. Activation of PPARα by fatty acid accumulation enhances fatty acid degradation and sulfatide synthesis. Tohoku J Exp Med 2016; 240(2): 113-22.
[http://dx.doi.org/10.1620/tjem.240.113] [PMID: 27644403]
[11]
Ohashi K, Munetsuna E, Yamada H, et al. High fructose consumption induces DNA methylation at PPARα and CPT1A promoter regions in the rat liver. Biochem Biophys Res Commun 2015; 468: 185-9.
[http://dx.doi.org/10.1016/j.bbrc.2015.10.134]
[12]
Hong F, Xu P, Zhai Y. The opportunities and challenges of peroxisome proliferator-activated receptors ligands in clinical drug discovery and development. Int J Mol Sci 2018; 2018: 19082189.
[http://dx.doi.org/10.3390/ijms19082189]
[13]
Abraham Domínguez-Avila J, González-Aguilar GA, Alvarez-Parrilla E, de la Rosa LA. Modulation of PPAR expression and activity in response to polyphenolic compounds in high fat diets. Int J Mol Sci 2017; 17(7): 1002.
[14]
Kumar SSD, Houreld NN, Abrahamse H. Therapeutic potential and recent advances of curcumin in the treatment of aging-associated diseases. Molecules 2018; 23(4): 835.
[15]
Hewlings S, Kalman D. Curcumin: A review of its effects on human health. MDPI AG 2017; 6: 92.
[http://dx.doi.org/10.3390/foods6100092]
[16]
Jin T, Song Z, Weng J, Fantus IG. Curcumin and other dietary polyphenols: Potential mechanisms of metabolic actions and therapy for diabetes and obesity. Am J Physiol Endocrinol Metab 2018; 314: E201-5.
[17]
Jin TR. Curcumin and dietary polyphenol research: Beyond drug discovery. Acta Pharmacol Sin 2018; 779-86.
[18]
Jiménez-Flores LM, López-Briones S, Macías-Cervantes MH, Ramírez-Emiliano J, Pérez-Vázquez V. A PPARγ, NF-κB and AMPK-dependent mechanism may be involved in the beneficial effects of curcumin in the diabetic db/db mice liver. Molecules 2014; 19(6): 8289-302.
[http://dx.doi.org/10.3390/molecules19068289] [PMID: 24945581]
[19]
Yoo SY, Ahn H, Park YK. High dietary fructose intake on cardiovascular disease related parameters in growing rats. Nutrients 2017; 9(1): 11.
[20]
Hurkman WJ, Tanaka CK. Solubilization of plant membrane proteins for analysis by two-dimensional gel electrophoresis. Plant Physiol 1986; 81(3): 802-6.
[http://dx.doi.org/10.1104/pp.81.3.802] [PMID: 16664906]
[21]
Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248-54.
[http://dx.doi.org/10.1016/0003-2697(76)90527-3] [PMID: 942051]
[22]
Pulido-Moran M, Moreno-Fernandez J, Ramirez-Tortosa C, Ramirez-Tortosa MC. Curcumin and health. Molecules 2016; 2016: 21030264.
[http://dx.doi.org/10.3390/molecules21030264]
[23]
Kelany ME, Hakami TM, Omar AH. Curcumin improves the metabolic syndrome in high-fructosediet-fed rats: Role of TNF-α, NF-κB, and oxidative stress. Can J Physiol Pharmacol 2017; 95: 140-50.
[PMID: 27901349]
[24]
Maithilikarpagaselvi N, Sridhar MG, Swaminathan RP, Zachariah B. Curcumin prevents inflammatory response, oxidative stress and insulin resistance in high fructose fed male Wistar rats: Potential role of serine kinases. Chem Biol Interact 2016; 244: 187-94.
[http://dx.doi.org/10.1016/j.cbi.2015.12.012] [PMID: 26713546]
[25]
Manzoni AG, Passos DF, da Silva JLG, et al. Rutin and curcumin reduce inflammation, triglyceride levels and ADA activity in serum and immune cells in a model of hyperlipidemia. Blood Cells Mol Dis 2019; 76: 13-21.
[http://dx.doi.org/10.1016/j.bcmd.2018.12.005]
[26]
Lewandowski ED, Fischer SK, Fasano M, et al. Acute liver carnitine palmitoyltransferase I overexpression recapitulates reduced palmitate oxidation of cardiac hypertrophy. Circ Res 2013; 112(1): 57-65.
[http://dx.doi.org/10.1161/CIRCRESAHA.112.274456] [PMID: 22982985]
[27]
Xie XW. Liquiritigenin attenuates cardiac injury induced by high fructose-feeding through fibrosis and inflammation suppression. Biomed Pharmacother Elsevier Masson SAS 2017; 86: 694-704.
[http://dx.doi.org/10.1016/j.biopha.2016.12.066] [PMID: 28039849]
[28]
Lone J, Choi JH, Kim SW, Yun JW. Curcumin induces brown fat-like phenotype in 3T3-L1 and primary white adipocytes. J Nutr Biochem 2016; 27: 193-202.
[29]
Chan MY, Zhao Y, Heng CK. Sequential responses to high-fat and high-calorie feeding in an obese mouse model. Obesity (Silver Spring) 2008; 16(5): 972-8.
[http://dx.doi.org/10.1038/oby.2008.32] [PMID: 18292748]
[30]
Bruce CR, Hoy AJ, Turner N, et al. Overexpression of carnitine palmitoyltransferase-1 in skeletal muscle is sufficient to enhance fatty acid oxidation and improve high-fat diet-induced insulin resistance. Diabetes 2009; 58(3): 550-8.
[http://dx.doi.org/10.2337/db08-1078] [PMID: 19073774]
[31]
Sodhi SS, Ghosh M, Song KD, et al. An approach to identify SNPs in the gene encoding acetyl-CoA acetyltransferase-2 (ACAT-2) and their proposed role in metabolic processes in pig. PLoS One 2014; 9: 102432.
[http://dx.doi.org/10.1371/journal.pone.0102432]

© 2024 Bentham Science Publishers | Privacy Policy