Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Jun 10;14:75.
doi: 10.1186/s12933-015-0237-9.

Protective Role of Oleic Acid Against Cardiovascular Insulin Resistance and in the Early and Late Cellular Atherosclerotic Process

Affiliations
Free PMC article

Protective Role of Oleic Acid Against Cardiovascular Insulin Resistance and in the Early and Late Cellular Atherosclerotic Process

Liliana Perdomo et al. Cardiovasc Diabetol. .
Free PMC article

Abstract

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.

Figures

Fig. 1
Fig. 1
Characterization of cardiovascular lines. a Western blot analysis against AgT and p53 to check the immortalization performed in neonatal cardiomyocyte lines. β-actin was used as charge control. b Characterization of neonatal cardiomyocytes with a specific marker as TnT by Western blot or by immunofluorescence. Characterization of ECs with specific markers as PECAM-1 or CD31 by flow cytometry (c) or vWF by immunofluorescence (d). Western blot analysis of insulin signalling in CMs (e, f) and in ECs (g). *p < 0.05 vs. control
Fig. 2
Fig. 2
Oleate did not induce cardiovascular insulin resistance. Western blot analysis of phosphorylation de Akt (T308), AMPK (T172), p42/44 (T202/Y204) and p70S6K (T389) induced by insulin (10nM, 10 min) in presence or absence of oleate (2 h) in CMs (a), ECs (b) and VSMCs (c). β-actin was used as charge control. *p < 0.05 vs. control
Fig. 3
Fig. 3
Palmitate induced cardiovascular insulin resistance. Western blot analysis (a) and its quantifications (b) of Akt phosphorylation (T308), p42/44 (T202/Y204) and p70S6K (T389) induced by insulin (10nM, 10 min) in presence or absence of oleate (2 h) in CMs, ECs and VSMCs. β-actin was used as charge control. *p < 0.05 vs. control; †p < 0.05 vs. stimulus
Fig. 4
Fig. 4
Oleate protected cardiovascular insulin resistance induced by TNF-α or palmitate. Western blot analysis of phosphorylation of Akt (T308) induced by insulin (10nM, 10 min) and /or palmitate (0.4 mM, 18 h) or TNF-α (10 ng/mL, 2 h) in presence or absence of oleate in CMs, ECs and VSMCs. β-actin was used as charge control. *p < 0.05 vs. control; †p < 0.05 vs. stimulus
Fig. 5
Fig. 5
Modulation of JNK-1/2 and NF-κB pathway by oleate. a Western blot analysis of JNK-1/2 phosphorylation in CMs, ECs and VSMCs. b Effect of oleate in the Ser and Tyr phosphorylation of IRS-1 in VSMCs. Effect of TNF-α or palmitate in IκBα levels in absence (c) or presence (d) of oleate in VSMCs. e Effect of parthenolide in the phosphorylation of Akt in VSMCs. β-actin was used as charge control
Fig. 6
Fig. 6
Effect of oleate in eNOS, ICAM-1 and MCP-1 mRNA expression in ECs. qRT-PCR analysis of eNOS (a), ICAM-1 (b) and MCP-1 (c) mRNA expression induced by TNF-α, IL-6 and IL-1β in presence or absence of oleate in ECs. *p < 0.05 vs. control; †p < 0.05 vs. stimulus
Fig. 7
Fig. 7
Effect of oleate in VSMCs proliferation. Rates of proliferation measured by BrdU incorporation in response to TNF-α, angiotensin II or palmitate in presence or absence of oleate. *p < 0.05 vs. control; †p < 0.05 vs. stimulus
Fig. 8
Fig. 8
Effect of oleate in VSMCs apoptosis. Effect of oleate in VSMCs apoptosis induced by TNF-α measured by cellular cycle (a) or by Western blot analysis of active caspase 3 (b) or induced by thapsigargin by Western blot analysis (c). *p < 0.05 vs. control; †p < 0.05 vs. stimulus. d Western blot analysis of PAI-1 levels induced by TNF-α at different time points. e Effect of oleate and parthenolide in PAI-1 levels induced by TNF-α. β-actin was used as charge control

Similar articles

See all similar articles

Cited by 23 articles

See all "Cited by" articles

References

    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. doi: 10.1074/jbc.M708700200. - DOI - PubMed
    1. 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. doi: 10.1074/jbc.M513304200. - DOI - PubMed
    1. 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. doi: 10.1172/JCI11559. - DOI - PMC - PubMed
    1. 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. doi: 10.1007/s12020-009-9283-y. - DOI - PubMed
    1. 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. - PubMed

Publication types

MeSH terms

Feedback