Dietary Improvement during Lactation Normalizes miR-26a, miR-222 and miR-484 Levels in the Mammary Gland, but Not in Milk, of Diet-Induced Obese Rats.

We aimed to evaluate in rats whether the levels of specific miRNA are altered in the mammary gland (MG) and milk of diet-induced obese dams, and whether improving maternal nutrition during lactation attenuates such alterations. Dams fed with a standard diet (SD) (control group), with a Western diet (WD) prior to and during gestation and lactation (WD group), or with WD prior to and during gestation but moved to SD during lactation (Rev group) were followed. The WD group showed higher miR-26a, miR-222 and miR-484 levels than the controls in the MG, but the miRNA profile in Rev animals was not different from those of the controls. The WD group also displayed higher miR-125a levels than the Rev group. Dams of the WD group, but not the Rev group, displayed lower mRNA expression levels of Rb1 (miR-26a's target) and Elovl6 (miR-125a's target) than the controls in the MG. The WD group also presented lower expression of Insig1 (miR-26a's target) and Cxcr4 (miR-222's target) than the Rev group. However, both WD and Rev animals displayed lower expression of Vegfa (miR-484's target) than the controls. WD animals also showed greater miR-26a, miR-125a and miR-222 levels in the milk than the controls, but no differences were found between the WD and Rev groups. Thus, implementation of a healthy diet during lactation normalizes the expression levels of specific miRNAs and some target genes in the MG of diet-induced obese dams but not in milk.