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

Abstract

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.

Milk Exosomal microRNAs: Postnatal Promoters of β Cell Proliferation but Potential Inducers of β Cell De-Differentiation in Adult Life

“…Preferential intake of n-3 PUFA may thus modify the m6A RNA methylation status of the β cell via miR-30b-mediated suppression of FTO [ 200 ]. Consumption of the “Cafeteria diet”—a standardized animal model of hypercaloric Western junk food [ 432 ]—during lactation (day 15) in rats, resulted in higher levels of miR-222 in rat milk compared to the miR-222 levels of the control animals [ 433 , 434 ]. Of note, serum exosomes enriched in miR-222 after bone marrow transplantation increased murine β cell proliferation in mice after STZ-induced β cell injury [ 435 ].…”

Early Life Programming of Adipose Tissue Remodeling and Browning Capacity by Micronutrients and Bioactive Compounds as a Potential Anti-Obesity Strategy

“…Interestingly, the offspring of dams fed the obesogenic diet, breastfed with lower levels of miR-26a, and showed a higher expression of Hmag1, Rb1, and Adam17 in retroperitoneal WAT compared to controls [165]. Notably, elevated levels of miR-222 in the mammary gland (at weaning) and in milk (on day 15 of lactation) were also observed in rat dams that were fed a Western diet from one month before gestation until the end of lactation [196]. This dietary condition was also associated with adverse programming effects on offspring [197].…”

“…This dietary condition was also associated with adverse programming effects on offspring [197]. Interestingly, the implementation of a healthy diet during lactation, which mitigated most of the detrimental programming effects in the offspring [197], also normalized the expression levels of miRNA-222 in both the mammary glands and milk to values of control rats [196].…”

miRNAs: From Master Regulators of Gene Expression to Biomarkers Involved in Intercellular Communication

“…The authors highlighted their possible role in shaping the development of the infant's immune systems and how they are associated with some diseases in both infants and mothers, including breast neoplasms and neonatal jaundice. Related to this aspect, Pomar et al [7] showed that changing the diet of diet-induced obese mice during lactation can reduce the abnormal level of miRNAs in their mammary glands, but not in their milk.…”