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  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id specific-use="scielo-v3" pub-id-type="publisher-id">r3j9Q8tC4QpvDRxxPQXnJBr</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2021001200726</article-id>
      <article-id pub-id-type="publisher-id">abc.20210717</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20210717</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Minieditorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Suplementa&#231;&#227;o de L-Carnitina no Cora&#231;&#227;o Diab&#233;tico</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Pereira</surname>
            <given-names>Filipe Welson Leal</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-4412-1990</contrib-id>
          <name>
            <surname>Paiva</surname>
            <given-names>Sergio Alberto Rupp de</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgdiv1">Faculdade de Medicina de Botucatu</institution>
        <institution content-type="orgname">Universidade Estadual Paulista</institution>
        <addr-line>
          <named-content content-type="city">Botucatu</named-content>
          <named-content content-type="state">SP</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (Unesp), Botucatu, SP &#8211; Brasil</institution>
      </aff>
      <author-notes>
        <corresp id="c01"> Correspond&#234;ncia: Sergio Alberto Rupp Paiva &#8226; Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (Unesp) - Av. Prof. M&#225;rio Rubens Guimar&#227;es Montenegro, s/n. CEP 18618-687, Campus de Botucatu, Botucatu, SP - Brasil E-mail: <email>sergio.paiva@unesp.br</email> </corresp>
      </author-notes>
      <pub-date date-type="pub" publication-format="electronic">
        <day>25</day>
        <month>10</month>
        <year>2021</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <month>10</month>
        <year>2021</year>
      </pub-date>
      <volume>117</volume>
      <issue>4</issue>
      <fpage>726</fpage>
      <lpage>727</lpage>
      <permissions>
        <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <license-p> 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. </license-p>
        </license>
      </permissions>
      <kwd-group xml:lang="pt">
        <kwd>Carnitina</kwd>
        <kwd>Metabolismo Energ&#233;tico</kwd>
        <kwd>Rea&#231;&#227;o em Cadeia da Polimerase</kwd>
      </kwd-group>
      <counts>
        <fig-count count="0"/>
        <table-count count="0"/>
        <equation-count count="0"/>
        <ref-count count="17"/>
        <page-count count="2"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <p>A carnitina &#233; um nutriente n&#227;o essencial, derivado de amino&#225;cidos, e sua principal fonte alimentar s&#227;o a carne vermelha, a carne de aves e os latic&#237;nios. Parte da carnitina pode ser produzida endogenamente a partir da lisina e da metionina, principalmente pelo f&#237;gado e rins.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Age sobretudo como cofator enzim&#225;tico para o transporte de &#225;cidos graxos de cadeia longa do citoplasma para o interior da mitoc&#244;ndria e subsequente degrada&#231;&#227;o para betaoxida&#231;&#227;o, e trata-se de uma via muito importante para metabolismo energ&#233;tico. Dessa forma, a carnitina &#233; essencial como combust&#237;vel para o m&#250;sculo, e mais de 95% da subst&#226;ncia &#233; encontrada no m&#250;sculo esquel&#233;tico.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> F&#237;gado, cora&#231;&#227;o, c&#233;rebro e rins det&#234;m o restante das reservas de carnitina corporal ou possuem condi&#231;&#245;es para s&#237;ntese,<sup><xref ref-type="bibr" rid="B1">1</xref></sup> e tal distribui&#231;&#227;o mostra a import&#226;ncia da carnitina nesses &#243;rg&#227;os. Estudos sobre a suplementa&#231;&#227;o de L-carnitina est&#227;o sendo desenvolvidos na sarcopenia,<sup><xref ref-type="bibr" rid="B2">2</xref></sup> em doen&#231;as hep&#225;ticas,<sup><xref ref-type="bibr" rid="B3">3</xref></sup> na insufici&#234;ncia card&#237;aca<sup><xref ref-type="bibr" rid="B4">4</xref></sup> e em doen&#231;as renais<sup><xref ref-type="bibr" rid="B5">5</xref></sup> e neurol&#243;gicas.<sup><xref ref-type="bibr" rid="B6">6</xref> , <xref ref-type="bibr" rid="B7">7</xref></sup></p>
    <p>A maioria dos estudos mostrou benef&#237;cio da L-carnitina nos fatores de risco cardiovascular, e sua suplementa&#231;&#227;o reduz hipertens&#227;o, hiperlipidemia, hiperglicemia, diabetes melito insulinodependente, resist&#234;ncia &#224; insulina, obesidade, inflama&#231;&#227;o e estresse oxidativo.<sup><xref ref-type="bibr" rid="B4">4</xref> , <xref ref-type="bibr" rid="B8">8</xref> - <xref ref-type="bibr" rid="B12">12</xref></sup></p>
    <p>Al&#233;m de atenuar os fatores de risco para a aterosclerose, a suplementa&#231;&#227;o de L-carnitina pode melhorar o metabolismo energ&#233;tico do cora&#231;&#227;o &#8220;diab&#233;tico&#8221;, por meio da manipula&#231;&#227;o dos grupos acetila e acila pela mitoc&#244;ndria. Desde que a L-carnitina &#233; respons&#225;vel por sua transfer&#234;ncia atrav&#233;s da membrana mitocondrial.<sup><xref ref-type="bibr" rid="B13">13</xref></sup> Outro mecanismo proposto &#233; o de que a suplementa&#231;&#227;o de L-carnitina pode melhorar o microambiente inflamat&#243;rio e oxidativo card&#237;aco causado pela hiperglicemia.<sup><xref ref-type="bibr" rid="B14">14</xref></sup> Nesse sentido, um artigo de revis&#227;o sistem&#225;tica e a metan&#225;lise de ensaios cl&#237;nicos randomizados mostraram que a suplementa&#231;&#227;o de L-carnitina foi associada a redu&#231;&#227;o de PCR, (interleucina 6 (IL-6), fator de necrose tumoral &#945; (TNF-&#945;) e malondialde&#237;do no plasma, e ao aumento das concentra&#231;&#245;es plasm&#225;ticas de super&#243;xido dismutase.<sup><xref ref-type="bibr" rid="B9">9</xref></sup></p>
    <p>No que diz respeito &#224; obesidade, observamos em revis&#227;o sistem&#225;tica que a suplementa&#231;&#227;o de L-carnitina reduziu peso corporal, &#237;ndice de massa do corpo (IMC) e massa gorda, e a an&#225;lise de subgrupo baseada na faixa de IMC basal dos participantes mostrou mais redu&#231;&#245;es em adultos com sobrepeso ou obesidade do que nos indiv&#237;duos com faixa de IMC normal.<sup><xref ref-type="bibr" rid="B12">12</xref></sup></p>
    <p>O artigo publicado na edi&#231;&#227;o dos Arquivos Brasileiros de Cardiologia tem como base obesidade, diabetes e inflama&#231;&#227;o.<sup><xref ref-type="bibr" rid="B15">15</xref></sup></p>
    <p>Os autores apresentaram resultados de estudo experimental, em que camundongos obesos com diabetes induzido receberam L-carnitina. Foram avaliadas a prote&#237;na da quemerina e o receptor CMKLRI (do ingl&#234;s <italic>chemokine like receptor 1</italic> ) no soro e nos tecidos card&#237;aco e adiposo, outros marcadores inflamat&#243;rios al&#233;m da resist&#234;ncia insul&#237;nica.<sup><xref ref-type="bibr" rid="B15">15</xref></sup></p>
    <p>A quemerina &#233; uma nova adipocina que participa dos est&#225;gios iniciais da inflama&#231;&#227;o aguda e participa no desenvolvimento de hipertens&#227;o, progress&#227;o de les&#245;es ateroscler&#243;ticas que possivelmente age por meio de seu receptor CMKLR1.<sup><xref ref-type="bibr" rid="B16">16</xref></sup> Os autores conseguiram mostrar associa&#231;&#227;o entre o consumo de L-carnitina e a redu&#231;&#227;o dos valores de quemerina s&#233;rica nos tecidos card&#237;aco e adiposo em camundongos diab&#233;ticos tratados, al&#233;m de reduzir valores de outros marcadores inflamat&#243;rios (IL 1&#946; e TNF- &#945;) ap&#243;s 4 semanas do tratamento. Observou-se, tamb&#233;m, que o grupo que sofreu a interven&#231;&#227;o apresentou melhor perfil de resist&#234;ncia insul&#237;nica.<sup><xref ref-type="bibr" rid="B15">15</xref></sup></p>
    <p>A redu&#231;&#227;o da quemerina e de outros marcadores inflamat&#243;rios podem estar mostrando a import&#226;ncia do processo inflamat&#243;rio no cora&#231;&#227;o diab&#233;tico; entretanto, ainda &#233; cedo para recomendar a suplementa&#231;&#227;o de L-carnitina. Existem estudos que mostram que produtos de degrada&#231;&#227;o da carnitina pela microbiota intestinal podem gerar o N-&#243;xido-trimetilamina (TMAO).<sup><xref ref-type="bibr" rid="B17">17</xref></sup> Observou-se em revis&#227;o sistem&#225;tica que o TMAO esteve associado, em modo &#8220;dose-dependente&#8221;, ao aumento de eventos cardiovasculares e mortalidade.<sup><xref ref-type="bibr" rid="B17">17</xref></sup> Dessa maneira, faltam estudos que levem a entendimento do papel da suplementa&#231;&#227;o da L-carnitina no tratamento adjuvante para a situa&#231;&#227;o do cora&#231;&#227;o diab&#233;tico.</p>
  </body>
  <back>
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    <fn-group>
      <fn fn-type="other">
        <p>
          <italic>Minieditorial referente ao artigo: Novo Efeito Cardioprotetor da L-Carnitina em Camundongos Obesos Diab&#233;ticos: Regula&#231;&#227;o da Express&#227;o de Quemerina e CMKLRI no Cora&#231;&#227;o e Tecidos Adiposos</italic>
        </p>
      </fn>
    </fn-group>
  </back>
  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Short Editorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>L-Carnitine Supplementation in the Diabetic Heart</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Pereira</surname>
            <given-names>Filipe Welson Leal</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-4412-1990</contrib-id>
          <name>
            <surname>Paiva</surname>
            <given-names>Sergio Alberto Rupp de</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1001">
        <label>1</label>
        <country country="BR">Brazil</country>
        <institution content-type="original">Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (Unesp), Botucatu, SP &#8211; Brazil</institution>
      </aff>
      <author-notes>
        <corresp id="c01001">Mailing Address: Sergio Alberto Rupp Paiva &#8226; Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (Unesp) - Av. Prof. M&#225;rio Rubens Guimar&#227;es Montenegro, s/n. Postal Code 18618-687, Campus de Botucatu, Botucatu, SP - Brazil E-mail: sergio.paiva@unesp.br</corresp>
      </author-notes>
      <kwd-group xml:lang="en">
        <kwd>Carnitine</kwd>
        <kwd>Energy Metabolism</kwd>
        <kwd>Polymerase Chain Reaction</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>Carnitine is a non-essential nutrient, which is derived from amino acids. The main food source of carnitine is red meat, poultry and dairy products. Part of the carnitine can be produced endogenously, from lysine and methionine mainly by the liver and kidneys.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> It acts primarily as an enzymatic cofactor for the transport of long-chain fatty acids from the cytoplasm into the mitochondria, and subsequent degradation to beta-oxidation, being a very important energy metabolism pathway. Therefore, carnitine is essential as fuel for muscles, and more than 95% of the total body carnitine is found in skeletal muscle.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> The liver, heart, brain and kidneys have the remainder of the body&#8217;s carnitine reserves or are able to synthesize it.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> This distribution shows the importance of carnitine in these organs. L-carnitine supplementation has been studied in sarcopenia,<sup><xref ref-type="bibr" rid="B2">2</xref></sup> in liver diseases,<sup><xref ref-type="bibr" rid="B3">3</xref></sup> in heart failure,<sup><xref ref-type="bibr" rid="B4">4</xref></sup> in kidney diseases<sup><xref ref-type="bibr" rid="B5">5</xref></sup> and in neurological diseases.<sup><xref ref-type="bibr" rid="B6">6</xref> , <xref ref-type="bibr" rid="B7">7</xref></sup></p>
      <p>Most studies have shown the benefit of L-carnitine on cardiovascular risk factors. L-carnitine supplementation reduces hypertension, hyperlipidemia, hyperglycemia, insulin-dependent diabetes mellitus, insulin resistance, obesity, inflammation and oxidative stress.<sup><xref ref-type="bibr" rid="B4">4</xref> , <xref ref-type="bibr" rid="B8">8</xref> - <xref ref-type="bibr" rid="B12">12</xref></sup></p>
      <p>In addition to attenuating risk factors for atherosclerosis, L-carnitine supplementation can improve the energy metabolism of the &#8220;diabetic&#8221; heart. The improvement can occur by normalizing the manipulation of the acetyl and acyl groups by the mitochondria, as L-carnitine is responsible for their transfer through the mitochondrial membrane.<sup><xref ref-type="bibr" rid="B13">13</xref></sup> Another proposed mechanism is that L-carnitine supplementation can improve the inflammatory and oxidative cardiac microenvironment caused by hyperglycemia.<sup><xref ref-type="bibr" rid="B14">14</xref></sup> Thus, a systematic review article and meta-analysis of randomized clinical trials showed that L-carnitine supplementation was associated with a reduction in the levels of CRP, Interleukin-6 (IL-6), tumor necrosis factor-&#945; (TNF-&#945;) and plasma malondialdehyde, and increased plasma levels of superoxide dismutase.<sup><xref ref-type="bibr" rid="B9">9</xref></sup></p>
      <p>Regarding obesity, a systematic review showed that L-carnitine supplementation reduced body weight, body mass index (BMI) and fat mass, and the subgroup analysis based on the participants&#8217; basal BMI range showed more reductions in overweight or obese adults than in those within the normal BMI range.<sup><xref ref-type="bibr" rid="B12">12</xref></sup></p>
      <p>The article published in this issue of the <italic>Arquivos Brasileiros de Cardiologia</italic> is based on obesity, diabetes and inflammation.<sup><xref ref-type="bibr" rid="B15">15</xref></sup></p>
      <p>The authors presented results of an experimental study, in which obese mice with induced diabetes received L-carnitine. Chemerin protein and Chemokine-like Receptor 1 (CMKLR1) levels in serum, cardiac and adipose tissue, as well as other inflammatory markers were evaluated, in addition to insulin resistance.<sup><xref ref-type="bibr" rid="B15">15</xref></sup></p>
      <p>Chemerin is a new adipokine that participates in the early stages of acute inflammation and participates in the development of hypertension, progression of atherosclerotic lesions, possibly acting through its CMKLR1 receptor.<sup><xref ref-type="bibr" rid="B16">16</xref></sup> The authors were able to demonstrate an association between L-carnitine consumption and a reduction in serum chemerin values and in cardiac and adipose tissue in treated diabetic mice, in addition to a reduction in the levels of other inflammatory markers (IL-1&#946; and TNF-&#945;) after 4 weeks of treatment. They also observed that the group submitted to the intervention had a better insulin resistance profile.<sup><xref ref-type="bibr" rid="B15">15</xref></sup></p>
      <p>The decrease in the levels of chemerin and other inflammatory markers may be showing the importance of the inflammatory process in the diabetic heart. However, it is still too early to recommend L-carnitine supplementation. Some studies have shown that carnitine degradation products by the intestinal microbiota can generate Trimethylamine N-oxide (TMAO).<sup><xref ref-type="bibr" rid="B17">17</xref></sup> A systematic review showed that TMAO was associated with an increase in cardiovascular events and mortality in a dose-dependent manner.<sup><xref ref-type="bibr" rid="B17">17</xref></sup> Thus, more studies are necessary to understand the role of L-carnitine supplementation in the adjuvant treatment of the diabetic heart.</p>
    </body>
    <back>
      <fn-group>
        <fn fn-type="other">
          <p>
            <italic>Short Editorial related to the article: Novel Cardioprotective Effect of L-Carnitine on Obese Diabetic Mice: Regulation of Chemerin and CMKLRI Expression in Heart and Adipose Tissues</italic>
          </p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
