Pomar, Catalina ASerra, FranciscaPalou, AndreuSanchez, Juana2024-09-182024-09-182021-10Pomar CA, Serra F, Palou A, Sanchez J. Lower miR-26a levels in breastmilk affect gene expression in adipose tissue of offspring. Faseb J. 2021 Oct;35(10):e21924.0892-6638https://hdl.handle.net/20.500.13003/19674https://hdl.handle.net/20.500.12105/23353Breastmilk miRNAs may act as epigenetic regulators of metabolism and energy homeostasis in offspring. Here, we aimed to investigate the regulatory effects of miR-26a on adipose tissue development. First, the 3T3-L1 cell model was used to identify putative target genes for miR-26a. Then, target genes were analysed in adipose tissue of offspring from dams that supplied lower levels of breastmilk miR-26a to determine whether miR-26a milk concentration might have a long-lasting impact on adipose tissue in the progeny. In the in vitro model, both over- and under-expression of miR-26a were induced by transfecting into 3T3-L1 with miR-26a mimic and inhibitor. Array analysis was performed after induction of miR-26a to ascertain the impact on mRNA target genes and influence of differentiation status. Focusing on genes related to adipose tissue development, transfection with miR-26a mimic reduced the expression of Pten, Hmga1, Stk11, Rb1, and Adam17 in both pre- and mature adipocytes. Data mostly confirmed the results found in the animal model. After weaning, descendants of cafeteria-fed dams breastfed with lower levels of miR-26a displayed greater expression of Hmag1, Rb1, and Adam17 in retroperitoneal white adipose tissue in comparison with controls. Hence, alterations in the amount of miR-26a supplied through milk during lactation is able to alter the expression of target genes in the descendants and may affect adipose tissue development. Thus, milk miR-26a may act as an epigenetic regulator influencing early metabolic program in the progeny, which emerges as a relevant component of an optimal milk composition for correct development.enghttp://creativecommons.org/licenses/by-nc-nd/4.0/BreastfeedingBreastmilkMilk's epigenetic regulatorsmiR-26aMammary Glands, AnimalMilkMicroRNAsFemaleAnimalsAdipose TissueCell DifferentiationGene Expression RegulationCell LineReproducibility of ResultsMiceresearch articleAttribution-NonCommercial-NoDerivatives 4.0 International345820593510e2192410.1096/fj.202100623R1530-6860Faseb Journalopen accessRegulación de la Expresión GénicaTejido AdiposoAnimalesDiferenciación CelularReproducibilidad de los ResultadosLecheFemeninoGlándulas Mamarias AnimalesRatonesLínea CelularMicroARNs2-s2.0-85115851797702238200019L2013818453