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The DNA methyltransferase inhibitor decitabine blunts the response to a high-animal fat and protein diet in mice.
Flores-Sierra, José de Jesús; Muciño-Arellano, Magaly Del Rosario; Romo-Morales, Gloria Del Carmen; Sánchez-Palafox, Jaime Eduardo; Correa-Navarro, Viridiana Abigail; Colín-Castelán, Dannia; Pérez-Vázquez, Victoriano; Rangel-Salazar, Rubén; Rivera-Bustamante, Rafael; de la Rocha, Carmen; Rodríguez-Ríos, Dalia; Trejo-Saavedra, Diana Lilia; Molina-Torres, Jorge; Ramírez-Chávez, Enrique; García-Rojas, Nancy Shyrley; Winkler, Robert; Lund, Gertrud; Zaina, Silvio.
Afiliação
  • Flores-Sierra JJ; Division of Health Sciences, Department of Medical Sciences, Leon Campus, University of Guanajuato, Leon, Mexico; Tecnológico Nacional de México/ITS de Purísima del Rincón, Purísima del Rincón, Guanajuato, Mexico.
  • Muciño-Arellano MDR; Division of Health Sciences, Department of Medical Sciences, Leon Campus, University of Guanajuato, Leon, Mexico.
  • Romo-Morales GDC; Division of Health Sciences, Department of Medical Sciences, Leon Campus, University of Guanajuato, Leon, Mexico.
  • Sánchez-Palafox JE; Division of Health Sciences, Department of Medical Sciences, Leon Campus, University of Guanajuato, Leon, Mexico.
  • Correa-Navarro VA; Division of Health Sciences, Department of Medical Sciences, Leon Campus, University of Guanajuato, Leon, Mexico.
  • Colín-Castelán D; Division of Health Sciences, Department of Medical Sciences, Leon Campus, University of Guanajuato, Leon, Mexico.
  • Pérez-Vázquez V; Division of Health Sciences, Department of Medical Sciences, Leon Campus, University of Guanajuato, Leon, Mexico.
  • Rangel-Salazar R; Division of Health Sciences, Department of Medical Sciences, Leon Campus, University of Guanajuato, Leon, Mexico.
  • Rivera-Bustamante R; Department of Genetic Engineering, CINVESTAV Irapuato Unit, Irapuato, Mexico.
  • de la Rocha C; Department of Genetic Engineering, CINVESTAV Irapuato Unit, Irapuato, Mexico.
  • Rodríguez-Ríos D; Department of Genetic Engineering, CINVESTAV Irapuato Unit, Irapuato, Mexico.
  • Trejo-Saavedra DL; Department of Genetic Engineering, CINVESTAV Irapuato Unit, Irapuato, Mexico.
  • Molina-Torres J; Department of Biotechnology and Biochemistry, CINVESTAV Irapuato Unit, Irapuato, Mexico.
  • Ramírez-Chávez E; Department of Biotechnology and Biochemistry, CINVESTAV Irapuato Unit, Irapuato, Mexico.
  • García-Rojas NS; Unit for Advanced Genomics, CINVESTAV, Irapuato, Mexico.
  • Winkler R; Unit for Advanced Genomics, CINVESTAV, Irapuato, Mexico.
  • Lund G; Department of Genetic Engineering, CINVESTAV Irapuato Unit, Irapuato, Mexico. Electronic address: gertrud.lund@cinvestav.mx.
  • Zaina S; Division of Health Sciences, Department of Medical Sciences, Leon Campus, University of Guanajuato, Leon, Mexico. Electronic address: szaina@ugto.mx.
J Lipid Res ; 65(8): 100586, 2024 Aug.
Article em En | MEDLINE | ID: mdl-38942113
ABSTRACT
Increasing evidence hints that DNA hypermethylation may mediate the pathogenic response to cardiovascular risk factors. Here, we tested a corollary of that hypothesis, that is, that the DNA methyltransferase inhibitor decitabine (Dec) ameliorates the metabolic profile of mice fed a moderately high-animal fat and protein diet (HAFPD), a proxy of cardiovascular risk-associated Western-type diet. HAFPD-fed mice were exposed to Dec or vehicle for eight weeks (8W set, 4-32/group). To assess any memory of past exposure to Dec, we surveyed a second mice set treated as 8W but HAFPD-fed for further eight weeks without any Dec (16W set, 4-20/group). In 8W, Dec markedly reduced HAFPD-induced body weight gain in females, but marginally in males. Characterization of females revealed that Dec augmented skeletal muscle lipid content, while decreasing liver fat content and increasing plasma nonesterified fatty acids, adipose insulin resistance, and-although marginally-whole blood acylcarnitines, compared to HAFPD alone. Skeletal muscle mitochondrial DNA copy number was higher in 8W mice exposed to HAFPD and Dec, or in 16W mice fed HAFPD only, relative to 8W mice fed HAFPD only, but Dec induced a transcriptional profile indicative of ameliorated mitochondrial function. Memory of past Dec exposure was tissue-specific and sensitive to both duration of exposure to HAFPD and age. In conclusion, Dec redirected HAFPD-induced lipid accumulation toward the skeletal muscle, likely due to augmented mitochondrial functionality and increased lipid demand. As caveat, Dec induced adipose insulin resistance. Our findings may help identifying strategies for prevention and treatment of lipid dysmetabolism.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dieta Hiperlipídica / Decitabina Limite: Animals Idioma: En Revista: J Lipid Res Ano de publicação: 2024 Tipo de documento: Article País de afiliação: México País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dieta Hiperlipídica / Decitabina Limite: Animals Idioma: En Revista: J Lipid Res Ano de publicação: 2024 Tipo de documento: Article País de afiliação: México País de publicação: Estados Unidos