Protective role of oleic acid against cardiovascular insulin resistance and in the early and late cellular atherosclerotic process

Cardiovascular Diabetology

Manuel Benito¹  Almudena Gómez-Hernández¹  Sabela Díaz-Castroverde¹  Óscar Escribano¹  Yolanda F. Otero¹  Nuria Beneit¹  Liliana Perdomo¹ 

[1] CIBER of Diabetes and Associated Metabolic Diseases, Madrid, Spain

关键词: Insulin resistance;    Atherosclerosis;    Fatty acids;   

Others  :  1216833
DOI  :  10.1186/s12933-015-0237-9

 received in 2015-03-10, accepted in 2015-05-29,  发布年份 2015

【 摘 要 】

Background

Several translational studies have identified the differential role between saturated and unsaturated fatty acids at cardiovascular level. However, the molecular mechanisms that support the protective role of oleate in cardiovascular cells are poorly known. For these reasons, we studied the protective role of oleate in the insulin resistance and in the atherosclerotic process at cellular level such as in cardiomyocytes (CMs), vascular smooth muscle cells (VSMCs) and endothelial cells (ECs).

Methods

The effect of oleate in the cardiovascular insulin resistance, vascular dysfunction, inflammation, proliferation and apoptosis of VSMCs were analyzed by Western blot, qRT-PCR, BrdU incorporation and cell cycle analysis.

Results

Palmitate induced insulin resistance. However, oleate not only did not induce cardiovascular insulin resistance but also had a protective effect against insulin resistance induced by palmitate or TNFα. One mechanism involved might be the prevention by oleate of JNK-1/2 or NF-κB activation in response to TNF-α or palmitate. Oleate reduced MCP-1 and ICAM-1 and increased eNOS expression induced by proinflammatory cytokines in ECs. Furthermore, oleate impaired the proliferation induced by TNF-α, angiotensin II or palmitate and the apoptosis induced by TNF-α or thapsigargin in VSMCs.

Conclusions

Our data suggest a differential role between oleate and palmitate and support the concept of the cardioprotector role of oleate as the main lipid component of virgin olive oil. Thus, oleate protects against cardiovascular insulin resistance, improves endothelial dysfunction in response to proinflammatory signals and finally, reduces proliferation and apoptosis in VSMCs that may contribute to an ameliorated atherosclerotic process and plaque stability.

【 授权许可】

   
2015 Perdomo et al.

【 图 表 】

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【 参考文献 】

• [1]Coll T, Eyre E, Rodríguez-Calvo R, Palomer X, Sánchez RM, Merlos M et al.. Oleate reverses palmitate-induced insulin resistance and inflammation in skeletal muscle cells. J Biol Chem. 2008; 283:11107-16.
• [2]Senn JJ. Toll-like receptor-2 is essential for the development of palmitate-induced insulin resistance in myotubes. J Biol Chem. 2006; 281:26865-26875.
• [3]Kim JK, Kim YJ, Fillmore JJ, Chen Y, Moore I, Lee J et al.. Prevention of fat-induced insulin resistance by salicylate. J Clin Invest. 2001; 108:437-46.
• [4]Zhang J, Wu W, Li D, Guo Y, Ding H. Overactivation of NF-κB impairs insulin sensitivity and mediates palmitate-induced insulin resistance in C2C12 skeletal muscle cells. Endocrine. 2010; 37:157-66.
• [5]Kern PA, Ranganathan S, Li C, Wood L, Ranganathan G. Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab. 2001; 280:E745-E751.
• [6]Lee KS, Kim J, Kwak SN, Lee KS, Lee DK, Ha KS et al.. Functional role of NF-κB in expression of human endothelial nitric oxide synthase. Biochem Biophys Res Commun. 2014; 448:101-7.
• [7]Yeh M, Leitinger N, de Martin R, Onai N, Matsushima K, Vora DK et al.. Increased transcription of IL-8 in endothelial cells is differentially regulated by TNF-alpha and oxidized phospholipids. Arterioscler Thromb Vasc Biol. 2001; 21:1585-91.
• [8]Hamaguchi E, Takamura T, Shimizu A, Nagai Y. Tumor necrosis factor-alpha and troglitazone regulate plasminogen activator inhibitor type 1 production through extracellular signal-regulated kinase- and nuclear factor-kappaB-dependent pathways in cultured human umbilical vein endothelial cells. J Pharmacol Exp Ther. 2003; 307:987-94.
• [9]Gorgani-Firuzjaee S, Ahmadi S, Meshkani R. Palmitate induces SHIP2 expression via the ceramide-mediated activation of NF-κB, and JNK in skeletal muscle cells. Biochem Biophys Res Commun. 2014; 450:494-9.
• [10]Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós F et al.. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013; 368:1279-90.
• [11]Mayneris-Perxachs J, Sala-Vila A, Chisaguano M, Castellote AI, Estruch R, Covas MI et al.. Effects of 1-year intervention with a mediterranean diet on plasma Fatty acid composition and metabolic syndrome in a population at high cardiovascular risk. PLoS One. 2014; 9(3):e85202.
• [12]Hlais S, El-Bistami D, El Rahi B, Mattar MA, Obeid OA. Combined fish oil and high oleic sunflower oil supplements neutralize their individual effects on the lipid profile of healthy men. Lipids. 2013; 48:853-61.
• [13]Pérez-Martínez P, García-Ríos A, Delgado-Lista J, Pérez-Jiménez F, López-Miranda J. Mediterranean diet rich in olive oil and obesity, metabolic syndrome and diabetes mellitus. Curr Pharm Des. 2011; 17:769-77.
• [14]Kwon B, Lee HK, Querfurth HW. Oleate prevents palmitate-induced mitochondrial dysfunction, insulin resistance and inflammatory signaling in neuronal cells. Biochim Biophys Acta. 1843; 2014:1402-13.
• [15]Salvadó L, Coll T, Gómez-Foix AM, Salmerón E, Barroso E, Palomer X et al.. Oleate prevents saturated-fatty-acid-induced ER stress, inflammation and insulin resistance in skeletal muscle cells through an AMPK-dependent mechanism. Diabetologia. 2013; 56:1372-82.
• [16]Hernández-Presa M, Bustos C, Ortego M, Tuñon J, Renedo G, Ruiz-Ortega M et al.. Angiotensin-converting enzyme inhibition prevents arterial nuclear factor-κB activation, monocyte chemoattractant protein-1 expression, and macrophage infiltration in a rabbit model of early accelerated atherosclerosis. Circulation. 1997; 95:1532-1541.
• [17]Escribano O, Guillén C, Nevado C, Gómez-Hernández A, Kahn CR, Benito M. Beta-Cell hyperplasia induced by hepatic insulin resistance: role of a liver-pancreas endocrine axis through insulin receptor A isoform. Diabetes. 2009; 58:820-8.
• [18]Gómez-Hernández A, Escribano Ó, Perdomo L, Otero YF, García-Gómez G, Fernández S et al.. Implication of insulin receptor A isoform and IRA/IGF-IR hybrid receptors in the aortic vascular smooth muscle cell proliferation: role of TNF-α and IGF-II. Endocrinology. 2013; 154:2352-64.
• [19]Gómez-Hernández A, Perdomo L, de las Heras N, Beneit N, Escribano O, Otero YF et al.. Antagonistic effect of TNF-alpha and insulin on uncoupling protein 2 (UCP-2) expression and vascular damage. Cardiovasc Diabetol. 2014; 13:108.
• [20]Sheehan M, Wong HR, Hake PW, Malhotra V, O’Connor M, Zingarelli B. Parthenolide, an inhibitor of the nuclear factor-kappaB pathway, ameliorates cardiovascular derangement and outcome in endotoxic shock in rodents. Mol Pharmacol. 2002; 61:953-63.
• [21]Martín-Ventura JL, Blanco-Colio LM, Muñoz-García B, Gómez-Hernández A, Arribas A, Ortega L et al.. NF-kappaB activation and Fas ligand overexpression in blood and plaques of patients with carotid atherosclerosis: potential implication in plaque instability. Stroke. 2004; 35:458-63.
• [22]Harari OA, Liao JK. NF-κB and innate immunity in ischemic stroke. Ann N Y Acad Sci. 2010; 1207:32-40.
• [23]Iwaki T, Urano T, Umemura K. PAI-1, progress in understanding the clinical problem and its aetiology. Br J Haematol. 2012; 157:291-8.
• [24]Reaven GM. Insulin resistance, the insulin resistance syndrome, and cardiovascular disease. Panminerva Med. 2005; 47:201-10.
• [25]Chavez JA, Holland WL, Bär J, Sandhoff K, Summers SA. Acid ceramidase overexpression prevents the inhibitory effects of saturated fatty acids on insulin signaling. J Biol Chem. 2005; 280:20148-53.
• [26]Lima-Leopoldo AP, Leopoldo AS, da Silva DC, do Nascimento AF, de Campos DH, Luvizotto RA et al.. Long-term obesity promotes alterations in diastolic function induced by reduction of phospholamban phosphorylation at serine-16 without affecting calcium handling. J Appl Physiol. 2014; 117:669-78.
• [27]Leopoldo AS, Lima-Leopoldo AP, Sugizaki MM, do Nascimento AF, de Campos DH, Luvizotto Rde A et al.. Involvement of L-type calcium channel and SERCA2a in myocardial dysfunction induced by obesity. J Cell Physiol. 2011; 226:2934-42.
• [28]Roy VK, Kumar A, Joshi P, Arora J, Ahanger AM. Plasma free Fatty Acid concentrations as a marker for acute myocardial infarction. J Clin Diagn Res. 2013; 7:2432-4.
• [29]Volpe CM, Nogueira-Machado JA. The dual role of free fatty acid signaling in inflammation and therapeutics. Recent Pat Endocr Metab Immune Drug Discov. 2013; 7:189-97.
• [30]Shen H, Eguchi K, Kono N, Fujiu K, Matsumoto S, Shibata M et al.. Saturated fatty acid palmitate aggravates neointima formation by promoting smooth muscle phenotypic modulation. Arterioscler Thromb Vasc Biol. 2013; 33:2596-607.
• [31]Harvey KA, Walker CL, Pavlina TM, Xu Z, Zaloga GP, Siddiqui RA. Long-chain saturated fatty acids induce pro-inflammatory responses and impact endothelial cell growth. Clin Nutr. 2010; 29:492-500.
• [32]Lai YH, Petrone AB, Pankow JS, Arnett DK, North KE, Ellison RC et al.. Association of dietary omega-3 fatty acids with prevalence of metabolic syndrome: the National Heart, Lung, and Blood Institute Family Heart Study. Clin Nutr. 2013; 32:966-9.
• [33]Moon HS, Batirel S, Mantzoros CS. Alpha linolenic acid and oleic acid additively down-regulate malignant potential and positively cross-regulate AMPK/S6 axis in OE19 and OE33 esophageal cancer cells. Metabolism. 2014; 63:1447-54.
• [34]Zhou YJ, Tang YS, Song YL, Li A, Zhou H, Li Y. Saturated fatty acid induces insulin resistance partially through nucleotide-binding oligomerization domain 1 signaling pathway in adipocytes. Chin Med Sci J. 2013; 28:211-7.
• [35]Gao D, Griffiths HR, Bailey CJ. Oleate protects against palmitate-induced insulin resistance in L6 myotubes. Br J Nutr. 2009; 102:1557-63.
• [36]Ramírez E, Klett-Mingo M, Ares-Carrasco S, Picatoste B, Ferrarini A, Rupérez FJ, Caro-Vadillo A, Barbas C, Egido J, Tuñón J, Lorenzo Ó. Eplerenone attenuated cardiac steatosis, apoptosis and diastolic dysfunction in experimental type-II diabetes. Cardiovasc Diabetol. 2013; 12:172. BioMed Central Full Text
• [37]Oliveira Junior SA, Padovani CR, Rodrigues SA, Silva NR, Martinez PF, Campos DH, Okoshi MP, Okoshi K, Dal-Pai M, Cicogna AC. Extensive impact of saturated fatty acids on metabolic and cardiovascular profile in rats with diet-induced obesity: a canonical analysis. Cardiovasc Diabetol. 2013; 12:65. BioMed Central Full Text
• [38]Wrede CE, Dickson LM, Lingohr MK, Briaud I, Rhodes CJ. Protein kinase B/Akt prevents fatty acid-induced apoptosis in pancreatic beta-cells (INS-1). J Biol Chem. 2002; 277:49676-84.
• [39]Chabowski A, Żendzian-Piotrowska M, Konstantynowicz K, Pankiewicz W, Mikłosz A, Łukaszuk B, Górski J. Fatty acid transporters involved in the palmitate and oleate induced insulin resistance in primary rat hepatocytes. Acta Physiol (Oxf). 2013; 207:346-57.
• [40]Medei E, Lima-Leopoldo AP, Pereira-Junior PP, Leopoldo AS, Campos DH, Raimundo JM et al.. Could a high-fat diet rich in unsaturated fatty acids impair the cardiovascular system? Can J Cardiol. 2010; 26:542-8.
• [41]Lee JY, Zhao L, Youn HS, Weatherill AR, Tapping R, Feng L et al.. Saturated fatty acid activates but polyunsaturated fatty acid inhibits Toll-like receptor 2 dimerized with Toll-like receptor 6 or 1. J Biol Chem. 2004; 279:16971-9.
• [42]Lee JY, Plakidas A, Lee WH, Heikkinen A, Chanmugam P, Bray G, Hwang DH. Differential modulation of Toll-like receptors by fatty acids: preferential inhibition by n-3 polyunsaturated fatty acids. J Lipid Res. 2003; 44:479-86.
• [43]Jang HJ, Kim HS, Hwang DH, Quon MJ, Kim JA. Toll-like receptor 2 mediates high-fat diet-induced impairment of vasodilator actions of insulin. Am J Physiol Endocrinol Metab. 2013; 304:E1077-88.
• [44]Perkins ND. Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat Rev Mol Cell Biol. 2007; 8:49-62.
• [45]Wen H, Gris D, Lei Y, Jha S, Zhang L, Huang MT, Brickey WJ, Ting JP. Fatty acid-induced NLRP3-ASC inflammasome activation interferes with insulin signaling. Nat Immunol. 2011; 12:408-15.
• [46]Yan Y, Jiang W, Spinetti T, Tardivel A, Castillo R, Bourquin C, Guarda G, Tian Z, Tschopp J, Zhou R. Omega-3 fatty acids prevent inflammation and metabolic disorder through inhibition of NLRP3 inflammasome activation. Immunity. 2013; 38:1154-63.
• [47]L’homme L, Esser N, Riva L, Scheen A, Paquot N, Piette J, Legrand-Poels S. Unsaturated fatty acids prevent activation of NLRP3 inflammasome in human monocytes/macrophages. J Lipid Res. 2013; 54:2998-3008.
• [48]Finucane OM, Lyons CL, Murphy AM, Reynolds CM, Klinger R, Healy NP et al.. Monounsaturated fatty acid-enriched high-fat diets impede adipose NLRP3 inflammasome-mediated IL-1β secretion and insulin resistance despite obesity. Diabetes. 2015; 64:2116-28.
• [49]Summers LK, Fielding BA, Bradshaw HA, Ilic V, Beysen C, Clark ML, Moore NR, Frayn KN. Substituting dietary saturated fat with polyunsaturated fat changes abdominal fat distribution and improves insulin sensitivity. Diabetologia. 2002; 45:369-77.
• [50]Perez-Martinez P, Garcia-Quintana JM, Yubero-Serrano EM, Tasset-Cuevas I, Tunez I, Garcia-Rios A, Delgado-Lista J, Marin C, Perez-Jimenez F, Roche HM, Lopez-Miranda J. Postprandial oxidative stress is modified by dietary fat: evidence from a human intervention study. Clin Sci (Lond). 2010; 119:251-61.
• [51]Karin M, Delhase M. The I kappa B kinase (IKK) and NF-kappa B: key elements of proinflammatory signalling. Semin Immunol. 2000; 12:85-98.
• [52]Brooks AR, Lelkes PI, Rubanyi GM. Gene expression profiling of human aortic endothelial cells exposed to disturbed flow and steady laminar flow. Physiol Genomics. 2002; 9:27-41.
• [53]Lamers D, Schlich R, Horrighs A, Cramer A, Sell H, Eckel J. Differential impact of oleate, palmitate, and adipokines on expression of NF-κB target genes in human vascular smooth muscle cells. Mol Cell Endocrinol. 2012; 362:194-201.
• [54]Murumalla RK, Gunasekaran MK, Padhan JK, Bencharif K, Gence L, Festy F et al.. Fatty acids do not pay the toll: effect of SFA and PUFA on human adipose tissue and mature adipocytes inflammation. Lipids Health Dis. 2012; 11:175. BioMed Central Full Text
• [55]Rath PC, Aggarwal BB. TNF-induced signaling in apoptosis. J Clin Immunol. 1999; 19:350-64.
• [56]Fan JH, Feng GG, Huang L, Tang GD, Jiang HX, Xu J. Naofen promotes TNF-α-mediated apoptosis of hepatocytes by activating caspase-3 in lipopolysaccharide-treated rats. World J Gastroenterol. 2014; 20:4963-71.
• [57]Staiger K, Staiger H, Weigert C, Haas C, Häring HU, Kellerer M. Saturated, but not unsaturated, fatty acids induce apoptosis of human coronary artery endothelial cells via nuclear factor-kappaB activation. Diabetes. 2006; 551:3121-6.
• [58]Al-Shudiefat AA, Sharma AK, Bagchi AK, Dhingra S, Singal PK. Oleic acid mitigates TNF-α-induced oxidative stress in rat cardiomyocytes. Mol Cell Biochem. 2013; 372:75-82.
• [59]Lytton J, Westlin M, Hanley MR. Thapsigargin inhibits the sarcoplasmic or endoplasmic reticulum Ca-ATPase family of calcium pumps. J Biol Chem. 1991; 266:17067-71.