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Syzygium cumini Leaf Extract Reverts Hypertriglyceridemia via Downregulation of the Hepatic XBP-1s/PDI/MTP Axis in Monosodium L-Glutamate-Induced Obese Rats.
França, Lucas Martins; Coêlho, Caio Fernando Ferreira; Freitas, Larissa Nara Costa; Souza, Ivana Letícia Santos; Chagas, Vinicyus Teles; Debbas, Victor; de Lima, Thais Martins; de Souza, Heraldo Possolo; Laurindo, Francisco Rafael Martins; Paes, Antonio Marcus de Andrade.
Afiliação
  • França LM; Laboratory of Experimental Physiology (LeFisio), Department of Physiological Sciences, Federal University of Maranhão, Av. dos Portugueses, 1966-Cidade Universitária Dom Delgado, São Luís, MA 65080-805, Brazil.
  • Coêlho CFF; Laboratory of Experimental Physiology (LeFisio), Department of Physiological Sciences, Federal University of Maranhão, Av. dos Portugueses, 1966-Cidade Universitária Dom Delgado, São Luís, MA 65080-805, Brazil.
  • Freitas LNC; Laboratory of Experimental Physiology (LeFisio), Department of Physiological Sciences, Federal University of Maranhão, Av. dos Portugueses, 1966-Cidade Universitária Dom Delgado, São Luís, MA 65080-805, Brazil.
  • Souza ILS; Laboratory of Experimental Physiology (LeFisio), Department of Physiological Sciences, Federal University of Maranhão, Av. dos Portugueses, 1966-Cidade Universitária Dom Delgado, São Luís, MA 65080-805, Brazil.
  • Chagas VT; Laboratory of Experimental Physiology (LeFisio), Department of Physiological Sciences, Federal University of Maranhão, Av. dos Portugueses, 1966-Cidade Universitária Dom Delgado, São Luís, MA 65080-805, Brazil.
  • Debbas V; Laboratory of Vascular Biology (LBV), Heart Institute, School of Medicine, University of São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 44-Cerqueira César, São Paulo, SP 05403-900, Brazil.
  • de Lima TM; Laboratory of Medical Investigation (LIM-51), Emergency Medicine Department, School of Medicine, University of São Paulo, Av. Dr. Arnaldo, 455-Cerqueira César, São Paulo, SP 01246-903, Brazil.
  • de Souza HP; Laboratory of Medical Investigation (LIM-51), Emergency Medicine Department, School of Medicine, University of São Paulo, Av. Dr. Arnaldo, 455-Cerqueira César, São Paulo, SP 01246-903, Brazil.
  • Laurindo FRM; Laboratory of Vascular Biology (LBV), Heart Institute, School of Medicine, University of São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 44-Cerqueira César, São Paulo, SP 05403-900, Brazil.
  • Paes AMA; Laboratory of Experimental Physiology (LeFisio), Department of Physiological Sciences, Federal University of Maranhão, Av. dos Portugueses, 1966-Cidade Universitária Dom Delgado, São Luís, MA 65080-805, Brazil.
Oxid Med Cell Longev ; 2019: 9417498, 2019.
Article em En | MEDLINE | ID: mdl-31015892
Syzygium cumini is used worldwide for the treatment of metabolic syndrome-associated outcomes. Previously, we described the antihypertriglyceridemic effect of the hydroethanolic extract of S. cumini leaf (HESc) in monosodium L-glutamate- (MSG-) induced obese rats. This study sought to investigate the molecular mechanisms underlying the antihypertriglyceridemic effect of HESc in MSG-obese rats. Newborn male Wistar rats were injected subcutaneously with MSG (4.0 g/kg/day, obese group) or saline 1.25% (1.0 mL/kg/day, lean group), from 2nd through 10th postnatal day. At 8 weeks old, obese rats started to be orally treated with HESc (0.5 or 1.0 g/kg/day, n = 7) or saline 0.9% (1 mL/kg/day, n = 7). Lean rats received saline solution (1 mL/kg/day, n = 7). Upon 8-week treatment, animals were euthanized for blood and tissue collection. Another set of adult nonobese Wistar rats was used for the assessment of HESc acute effects on Triton WR1339-induced hypertriglyceridemia. HESc reduced weight gain, as well as adipose tissue fat pads, without altering food intake of obese rats. HESc restored fasting serum glucose, triglycerides, total cholesterol, and free fatty acids, as well as insulin sensitivity, to levels similar to lean rats. Additionally, HESc halved the triglyceride content into very low-density lipoprotein particles, as well as healed liver steatosis, in obese rats. Hepatic protein expression of the endoplasmic reticulum chaperone GRP94 was decreased by HESc, which also downregulated the hepatic triglyceride secretion pathway by reducing the splicing of X-box binding protein 1 (XBP-1s), as well as protein disulfide isomerase (PDI) and microsomal triglyceride transfer protein (MTP) translational levels. This action was further corroborated by the acute inhibitory effect of HESc on triglyceride accumulation on Triton WR1339-treated rats. Our data support the downregulation of the XBP-1s/PDI/MTP axis in the liver of MSG-obese rats as a novel feasible mechanism for the antihypertriglyceridemic effect promoted by the polyphenolic phytocomplex present in S. cumini leaf.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Extratos Vegetais / Hipertrigliceridemia / Transdução de Sinais / Regulação para Baixo / Folhas de Planta / Syzygium / Fígado / Obesidade Limite: Animals Idioma: En Revista: Oxid Med Cell Longev Assunto da revista: METABOLISMO Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
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XML
PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Extratos Vegetais / Hipertrigliceridemia / Transdução de Sinais / Regulação para Baixo / Folhas de Planta / Syzygium / Fígado / Obesidade Limite: Animals Idioma: En Revista: Oxid Med Cell Longev Assunto da revista: METABOLISMO Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos