The DNA methyltransferase inhibitor decitabine blunts the response to a high-animal fat and protein diet in mice

José de Jesús Flores Sierra, Magaly del Rosario Muciño Arellano, Gloria del Carmen Romo Morales, Jaime Eduardo Sánchez Palafox, Viridiana Abigail Correa Navarro, Dannia Colín Castelán, Victoriano Pérez Vázquez, Rubén Rangel Salazar, Rafael Rivera Bustamante, Carmen de la Rocha, Dalia Rodríguez Ríos, Diana Lilia Trejo Saavedra, Jorge Molina Torres, Enrique Ramírez Chávez, Nancy Shyrley García Rojas, Robert Winkler, Gertrud Lund, Silvio Zaina

Te invitamos a leer el artículo "The DNA methyltransferase inhibitor decitabine blunts the response to a high-animal fat and protein diet in mice" publicado en "Journal of Lipid Research", en el que colaboraron el Dr. Rafael Rivera Bustamante, el Dr. Jorge Molina Torres y la Dra. Gertrud Lund de Cinvestav Irapuato.

Autores:

José de Jesús Flores Sierra, Magaly del Rosario Muciño Arellano, Gloria del Carmen Romo Morales, Jaime Eduardo Sánchez Palafox,  Viridiana Abigail Correa Navarro,  Dannia Colín Castelán,  Victoriano Pérez Vázquez,  Rubén Rangel Salazar,  Rafael Rivera Bustamante,  Carmen de la Rocha,  Dalia Rodríguez Ríos,  Diana Lilia Trejo Saavedra,  Jorge Molina Torres, Enrique Ramírez Chávez,  Nancy Shyrley García Rojas, Robert Winkler,  Gertrud Lund,  Silvio Zaina

Resumen:

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.