Arq Bras CardiolabcArquivos Brasileiros de CardiologiaArq. Bras. Cardiol.0066-782X1678-4170Sociedade Brasileira de Cardiologia - SBC9X6prbkKf8WnKDGGzLRhPwPS0066-782X201900120112810.5935/abc.20190228Short EditorialPPARβ/δ: Benefits in Coronary Artery Disease and Beyond0000-0001-5118-3204LealViviane O.Universidade Federal FluminenseNiteróiRJBrazilUniversidade Federal Fluminense, Niterói, RJ - BrazilMailing Address: Viviane O. Leal, Rua Mario dos Santos Braga, 30. Campus do Valonguinho, Faculdade de Nutrição, 4° Andar. Postal Code 24020-140. Centro, Niterói, RJ - Brazil E-mail: vivianeoleal@yahoo.com.br2122019122019113611281128This 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.KeywordsCoronary Artery DiseaseOxidative StrssInflammation, ObesityHypertensionDyslipidemiasRisk Factors/prevalenceMyocardial InfarctionHeart Failure
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
References1. Hong F, Pan S, Guo Y, Xu P , Zhai Y. PPARs as nuclear receptors for nutrient and energy metabolism. Molecules. 2019;24(14):E2545.HongFPanSGuoYXuPZhaiYPPARs as nuclear receptors for nutrient and energy metabolismMolecules20192414E25452. 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.BarbosaJEStockler-PintoMBCruzBOSilvaACTAnjosJSMesquitaCTNrf2, NF-?B and PPARß/d mRNA expression profile in patients with coronary artery diseaseArq Bras Cardiol20191136112111273. 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.PalomerXBarrosoEZareiMBotteriGVázquez-CarreraMPPARß/d and lipid metabolism in the heartBiochim Biophys Acta2016186110156915784 The Lancet Global Health. Getting to the hearth of non-communicable diseases. Lancet Glob Health. 2018;6(9):e933.The Lancet Global HealthGetting to the hearth of non-communicable diseasesLancet Glob Health201869e9335. 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.PalomerXBarrosoEPizarro-DelgadoJPenaLBotteriGZareiMPPARß/d: a key therapeutic target in metabolic disordersInt J Mol Sci2018193e9136. 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.LinHVFrasettoAKowalicEJJrNawrockiARLuMMKosinskiJRButyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanismsPlos One201274e352407. Grygiel-Górniak B. Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications - a review. Nut J. 2014; 13: 17.Grygiel-GórniakBPeroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications - a reviewNut J20141317178. 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.EsgalhadoMStenvinkelPMafraDNonpharmacologic strategies to modulate nuclear fator erythroid 2-related fator 2 pathway in chronic kidney diseaseJ Ren Nutr201702142742822919. 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.SchnuckJKGouldLMParryHAJohnsonMAGannonNPSunderlandKLMetabolic effects of physiological levels of caffeine in myotubesJ Physiol Biochem2018741354510. 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.Palacios-GonzalezBZarain-HerzbergAFlores-GlaiciaINoriegaLGAlemán-EscondrillasGZarinanTGenistein stimulates fatty acid oxidation in a leptina receptor-independent manner through the JAK2mediated phosphorylation and activation of AMPK in skeletal muscleBiochim Biophys Acta2014184113214011. 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.EcheverríaFOrtizMValenzuelaRVidelaLALong-chain polyunsaturated fatty acids regulation of PPARs, signaling: relationshiP to tissue development and agingProstaglandins Leukot Essent Fatty Acids2016111142834MinieditorialPPARβ/δ: Benefícios na Doença Arterial Coronariana e Além0000-0001-5118-3204LealViviane O.Universidade Federal Fluminense, Niterói, RJ - BrasilCorrespondência: Viviane O. Leal, Rua Mario dos Santos Braga, 30. Campus do Valonguinho, Faculdade de Nutrição, 4° Andar. CEP 24020-140. Centro, Niterói, RJ - Brasil E-mail: vivianeoleal@yahoo.com.brPalavras-chaveDoença da Artéria CoronarianaEstresse OxidativoInflamaçãoObesidadeHipertensãoDislipidemiasFatores de Risco/prevalênciaInfarto do MiocárdioInsuficiência Cardíaca
Os receptores ativados por proliferadores de peroxissoma (PPARs) são receptores nucleares que participam do metabolismo de nutrientes e energia.1 Em um artigo recente intitulado “Perfil da Expressão do mRNA do Nrf2, NF-κB e PPARβ/δ em Pacientes com Doença Arterial Coronariana (DAC)”, Barbosa et al. verificaram que a expressão do PPARβ/δ era mais alta nos pacientes com DAC quando comparados aos pacientes sem DAC.2
Além dos efeitos protetores do coração associados à melhora da função cardíaca e melhorias na progressão patológica da hipertrofia cardíaca, insuficiência cardíaca, dano oxidativo cardíaco, lesão de isquemia-reperfusão, disfunção cardíaca lipotóxica e inflamação cardíaca induzida por lipídios,3 outras funções do PPARβ/δ merecem ser consideradas no amplo contexto dos distúrbios cardiovasculares.
A obesidade e a dislipidemia são fatores de risco para doenças cardiovasculares4 e, nesse sentido, a modulação do PPARβ/δ pode ser interessante, pois está associada à melhora do catabolismo dos ácidos graxos (AG) no músculo esquelético ou a alternância do tipo de fibra muscular durante o metabolismo oxidativo.1,5 A ativação do PPARβ/δ também reduz a proliferação e diferenciação de pré-adipócitos e atenua a adipogênese hipertrófica disfuncional mediada pela angiotensina II e inibe a inflamação no tecido adiposo.5 Além disso, no intestino, o PPARβ/δ pode induzir a produção de ácidos graxos de cadeia curta (SCFA)1 e o butirato e o propionato, dois SCFA, foram associados à redução na ingestão de alimentos.6 Além disso, o PPARβ/δ melhora a oxidação hepática dos AG, o que diminui a disponibilidade de lípides para a síntese de triglicérides e altera a expressão de várias apoproteínas,5 contribuindo para elevar os níveis plasmáticos de lipoproteína de alta densidade e diminuir os níveis de lipoproteína de baixa densidade.1
Assim, o PPARβ/δ pode ser um alvo potencial em distúrbios metabólicos.5 Portanto, uma pergunta é pertinente: como modular o PPARβ/δ? No grupo de ligantes naturais, esse subtipo é ativado pela carbaprostaciclina, componentes da lipoproteína de muito baixa densidade e AG insaturados.7
Infelizmente, o PPARβ/δ não tem sido tão intensamente estudado quanto os subtipos α e γ7 e pouco se sabe sobre seus potenciais ativadores naturais, mesmo no caso de AG insaturados, que podem ser facilmente obtidos pela dieta e suplementos. Assim, aguardemos ansiosamente por esta resposta: é possível modular o PPARβ/δ através de compostos bioativos dietéticos? Estratégias não farmacológicas para modular outros fatores nucleares, como o fator nuclear eritroide 2 relacionado ao fator 2 (Nrf2) já foram indicadas8 e o mesmo se deseja para o PPARβ/δ. Cafeína,9 genisteína10 e padrão de dieta não ocidental11 já parecem promissores.
Minieditorial referente ao artigo: Perfil da Expressão do mRNA do Nrf2, NF-κB e PPARβ/δ em Pacientes com Doença Arterial Coronariana