PPARβ/δ: Benefits in Coronary Artery Disease and Beyond

Leal, Viviane O.

doi:10.5935/abc.20190228

Keywords
Coronary Artery Disease; Oxidative Strss; Inflammation, Obesity; Hypertension; Dyslipidemias; Risk Factors/prevalence; Myocardial Infarction; Heart Failure

Palavras-chave
Doença da Artéria Coronariana; Estresse Oxidativo; Inflamação; Obesidade; Hipertensão; Dislipidemias; Fatores de Risco/prevalência; Infarto do Miocárdio; Insuficiência Cardíaca

Keywords
Coronary Artery Disease; Oxidative Strss; Inflammation, Obesity; Hypertension; Dyslipidemias; Risk Factors/prevalence; Myocardial Infarction; Heart Failure

Palavras-chave
Doença da Artéria Coronariana; Estresse Oxidativo; Inflamação; Obesidade; Hipertensão; Dislipidemias; Fatores de Risco/prevalência; Infarto do Miocárdio; Insuficiência Cardíaca

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that participate in nutrient and energy metabolism.¹ In a recent paper entitled “Nrf2, NF-κB and PPAR β/δ mRNA expression profile in patients with coronary artery disease” (CAD), Barbosa et al. found that PPARβ/δ was highest expressed in the CAD patients when compared to patients without CAD.² Beyond its heart-protective effects associated to improvement of cardiac function and amelioration, the pathological progression of cardiac hypertrophy, heart failure, cardiac oxidative damage, ischemia-reperfusion injury, lipotoxic cardiac disfunction and lipid-induced cardiac inflammation,³ others functions PPARβ/δ deserve be considered in the wide context of the cardiovascular disorders.

Obesity and dyslipidemia are risk factors for cardiovascular disease⁴ and, in this sense, the modulation of PPARβ/δ can be interesting because it is associated with the improvement of fatty acid (FA) catabolism in skeletal muscle or alternating fibre type muscle during oxidative metabolism.¹^,⁵ PPARβ/δ activation also reduces pre-adipocyte proliferation and differentiation, and attenuates angiotensin II-mediated dysfunctional hypertrophic adipogenesis and inhibits inflammation in adipose tissue.⁵ Besides that, in the intestine, PPARβ/δ can induce the production of short-chain fatty acid (SCFA) production¹ and butyrate and propionate, two SCFA, were associated with reduction in food intake.⁶ Moreover, PPARβ/δ improves hepatic FA oxidation which decreases the lipids availability for triglycerides synthesis and changes the expression of several apoproteins,⁵ contributing for elevating plasma levels of high-density lipoprotein and decline levels of low-density lipoprotein.¹

Thus, PPARβ/δ can be a potential target in metabolic disorders.⁵ So, a question is pertinent: how to modulate PPARβ/δ? In the grouP of natural ligands, this subtype is activated by carbaprostacyclin, components of very low-density lipoprotein and unsaturated FAs.⁷

Unfortunately, PPARβ/δ has not been so intensely studied like the subtypes α and γ⁷ and little is known about the potential natural activators, even in the case of unsaturated FAs that can be easily obtained by diet and supplements. So, let's look forward to this answer: it is possible to modulate PPARβ/δ by dietetic bioactive compounds? Nonpharmacologic strategies to modulate other nuclear factors, such as nuclear factor erythroid 2-related factor 2 (Nrf2), been pointed⁸ and it is wanted to the same with PPARβ/δ. Caffeine,⁹ genistein¹⁰ and non-occidental diet pattern¹¹ already look promising.

Short Editorial related to the article: Nrf2, NF-κB and PPARβ/δ mRNA Expression Profile in Patients with Coronary Artery Disease

References

¹ Hong F, Pan S, Guo Y, Xu P , Zhai Y. PPARs as nuclear receptors for nutrient and energy metabolism. Molecules. 2019;24(14):E2545.
² Barbosa JE, Stockler-Pinto MB, Cruz BO, Silva ACT, Anjos JS, Mesquita CT, et al. Nrf2, NF-?B and PPARß/d mRNA expression profile in patients with coronary artery disease. Arq Bras Cardiol. 2019; 113(6):1121-1127.
³ Palomer X, Barroso E, Zarei M, Botteri G, Vázquez-Carrera M. PPARß/d and lipid metabolism in the heart. Biochim Biophys Acta.2016;1861(10):1569-78.
⁴ The Lancet Global Health. Getting to the hearth of non-communicable diseases. Lancet Glob Health. 2018;6(9):e933.
⁵ Palomer X, Barroso E, Pizarro-Delgado J, Pena L, Botteri G, Zarei M, et al. PPARß/d: a key therapeutic target in metabolic disorders. Int J Mol Sci. 2018; 19(3):e913.
⁶ Lin HV, Frasetto A, Kowalic EJ Jr, Nawrocki AR, Lu MM, Kosinski JR, et al. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. Plos One. 2012;7(4):e35240.
⁷ Grygiel-Górniak B. Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications - a review. Nut J. 2014; 13: 17.
⁸ Esgalhado M, Stenvinkel P , Mafra D. Nonpharmacologic strategies to modulate nuclear fator erythroid 2-related fator 2 pathway in chronic kidney disease. J Ren Nutr. 2017 Feb 14;27(4):282-91.
⁹ Schnuck JK, Gould LM, Parry HA, Johnson MA, Gannon NP , Sunderland KL, et al. Metabolic effects of physiological levels of caffeine in myotubes. J Physiol Biochem. 2018;74(1):35-45.
¹⁰ Palacios-Gonzalez B, Zarain-Herzberg A, Flores-Glaicia I, Noriega LG, Alemán-Escondrillas G, Zarinan T, et al. Genistein stimulates fatty acid oxidation in a leptina receptor-independent manner through the JAK2mediated phosphorylation and activation of AMPK in skeletal muscle. Biochim Biophys Acta. 2014;184(1):132-40.
¹¹ Echeverría F, Ortiz M, Valenzuela R, Videla LA. Long-chain polyunsaturated fatty acids regulation of PPARs, signaling: relationshiP to tissue development and aging. Prostaglandins Leukot Essent Fatty Acids. 2016 Nov;114:28-34.

Publication Dates

Publication in this collection
2 Dec 2019
Date of issue
Dec 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

[1] ¹ Hong F, Pan S, Guo Y, Xu P , Zhai Y. PPARs as nuclear receptors for nutrient and energy metabolism. Molecules. 2019;24(14):E2545.

[2] ² Barbosa JE, Stockler-Pinto MB, Cruz BO, Silva ACT, Anjos JS, Mesquita CT, et al. Nrf2, NF-?B and PPARß/d mRNA expression profile in patients with coronary artery disease. Arq Bras Cardiol. 2019; 113(6):1121-1127.

[3] ³ Palomer X, Barroso E, Zarei M, Botteri G, Vázquez-Carrera M. PPARß/d and lipid metabolism in the heart. Biochim Biophys Acta.2016;1861(10):1569-78.

[4] ⁴ The Lancet Global Health. Getting to the hearth of non-communicable diseases. Lancet Glob Health. 2018;6(9):e933.

[5] ⁵ Palomer X, Barroso E, Pizarro-Delgado J, Pena L, Botteri G, Zarei M, et al. PPARß/d: a key therapeutic target in metabolic disorders. Int J Mol Sci. 2018; 19(3):e913.

[6] ⁶ Lin HV, Frasetto A, Kowalic EJ Jr, Nawrocki AR, Lu MM, Kosinski JR, et al. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. Plos One. 2012;7(4):e35240.

[7] ⁷ Grygiel-Górniak B. Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications - a review. Nut J. 2014; 13: 17.

[8] ⁸ Esgalhado M, Stenvinkel P , Mafra D. Nonpharmacologic strategies to modulate nuclear fator erythroid 2-related fator 2 pathway in chronic kidney disease. J Ren Nutr. 2017 Feb 14;27(4):282-91.

[9] ⁹ Schnuck JK, Gould LM, Parry HA, Johnson MA, Gannon NP , Sunderland KL, et al. Metabolic effects of physiological levels of caffeine in myotubes. J Physiol Biochem. 2018;74(1):35-45.

[10] ¹⁰ Palacios-Gonzalez B, Zarain-Herzberg A, Flores-Glaicia I, Noriega LG, Alemán-Escondrillas G, Zarinan T, et al. Genistein stimulates fatty acid oxidation in a leptina receptor-independent manner through the JAK2mediated phosphorylation and activation of AMPK in skeletal muscle. Biochim Biophys Acta. 2014;184(1):132-40.

[11] ¹¹ Echeverría F, Ortiz M, Valenzuela R, Videla LA. Long-chain polyunsaturated fatty acids regulation of PPARs, signaling: relationshiP to tissue development and aging. Prostaglandins Leukot Essent Fatty Acids. 2016 Nov;114:28-34.