| Autor: |
de la Rocha C; Department of Genetic Engineering, CINVESTAV Irapuato Unit, Irapuato 36500, Mexico., Rodríguez-Ríos D; Department of Genetic Engineering, CINVESTAV Irapuato Unit, Irapuato 36500, Mexico., Ramírez-Chávez E; Department of Biotechnology and Biochemistry, CINVESTAV Irapuato Unit, Irapuato 36500, Mexico., Molina-Torres J; Department of Biotechnology and Biochemistry, CINVESTAV Irapuato Unit, Irapuato 36500, Mexico., de Jesús Flores-Sierra J; Department of Medical Sciences, Division of Health Sciences, León Campus, University of Guanajuato, León 37000, Mexico., Orozco-Castellanos LM; Department of Pharmacology, Division of Natural and Exact Sciences, Guanajuato Campus, University of Guanajuato, Guanajuato 36000, Mexico., Galván-Chía JP; Department of Pharmacology, Division of Natural and Exact Sciences, Guanajuato Campus, University of Guanajuato, Guanajuato 36000, Mexico., Sánchez AV; Department of Genetic Engineering, CINVESTAV Irapuato Unit, Irapuato 36500, Mexico., Zaina S; Department of Medical Sciences, Division of Health Sciences, León Campus, University of Guanajuato, León 37000, Mexico., Lund G; Department of Genetic Engineering, CINVESTAV Irapuato Unit, Irapuato 36500, Mexico. |
| Abstrakt: |
Apart from the known associations between arachidonic acid (AA), weight gain, and neurological and immune function, AA exposure leads to alterations in global and gene-specific DNA methylation (DNAm) and fatty acid (FA) content in human cultured cells. However, it is unknown as to whether the latter effects occur in vivo and are maintained over extended periods of time and across generations. To address this issue, we asked whether AA supplementation for three consecutive generations (prior to coitus in sires or in utero in dams) affected offspring growth phenotypes, in addition to liver DNAm and FA profiles in mice. Twelve-week-old BALB/c mice were exposed daily to AA dissolved in soybean oil (vehicle, VH), or VH only, for 10 days prior to mating or during the entire pregnancy (20 days). On average, 15 mice were supplemented per generation, followed by analysis of offspring body weight and liver traits (x average = 36 and 10 per generation, respectively). Body weight cumulatively increased in F2 and F3 offspring generations and positively correlated with milligrams of paternal or maternal offspring AA exposure. A concomitant increase in liver weight was observed. Notably, akin to AA-challenged cultured cells, global DNAm and cis-7-hexadecenoic acid (16:1n-9), an anti-inflammatory FA that is dependent on stearoyl-CoA desaturase 1 (SCD1) activity, increased with milligrams of AA exposure. In accordance, liver Scd1 promoter methylation decreased with milligrams of germline AA exposure and was negatively correlated with liver weight. Our results show that mice retain cellular memories of AA exposure across generations that could potentially be beneficial to the innate immune system. |
