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00925njm 22002777a 4500 dc Pomar, Catalina A author Serra, Francisca author Palou, Andreu author Sanchez, Juana author 2021-10 Breastmilk 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. Pomar 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. 0892-6638 https://hdl.handle.net/20.500.13003/19674 https://hdl.handle.net/20.500.12105/23353 34582059 10.1096/fj.202100623R 1530-6860 Faseb Journal 2-s2.0-85115851797 702238200019 L2013818453 Breastfeeding Breastmilk Milk's epigenetic regulators miR-26a Lower miR-26a levels in breastmilk affect gene expression in adipose tissue of offspring