Breast Milk MicroRNAs Related to Leptin and Adiponectin Function Can Be Modulated by Maternal Diet and Influence Offspring Phenotype in Rats

Abstract

There is evidence of the role of milk components in the metabolic programming of offspring. Here, we aimed to investigate the effects of a diet during lactation on breast milk leptin, adiponectin, and related miRNAs’ expression, and their impact on dams and their offspring. Dams were fed a control diet (controls) or a diet enriched with oleic acid, betaine, and leucine (TX) throughout lactation. A TX diet promoted higher leptin at lactation day (LD) five and lower adiponectin on LD15 (vs. controls) in milk, resulting in increased leptin to adiponectin (L/A) ratio throughout lactation. Moreover, TX diet reduced milk levels of miR-27a, miR-103, miR-200a, and miR-222. Concerning TX offspring, higher body fat was early observed and maintained into adult life, accompanied by higher HOMA-IR than controls at three months of age. Offspring body fat content in adulthood correlated positively with milk L/A ratio at LD15 and negatively with miRNAs modulated by the TX diet. In conclusion, maternal diet during lactation can modulate leptin and adiponectin interplay with miRNAs in milk, setting up the metabolic programming of the offspring. Better knowledge about the influence of diet on this process is necessary to promote a healthy adult life in the progeny.

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

“…However, the potential impact of the L/A ratio in milk on the long-term metabolic health of infants has been barely explored. In rats, the milk L/A ratio at day 15 of lactation positively correlated with the body fat mass of female offspring in adulthood, whereas absolute levels of both hormones per se did not show significant correlations [163]. A similar trend was observed in males.…”

“…These changes could be related to metabolic alterations observed in the offspring, which displayed increased body fat and HOMA-IR. Body fat content in adulthood was negatively associated with the levels of these miRNAs in milk [163].…”

“…Interestingly, many adipogenesisrelated miRNAs are found in milk, increasing the interest regarding their role as modulators of the reduced risk of obesity associated with breastfeeding. Although it is difficult to establish a direct cause-effect relationship between the effects of miRNAs supplied through milk on the AT development of newborns and the metabolic programming of obesity risk, several human studies and animal models have suggested this possibility [161][162][163][164][165][166][167][168][169].…”

A Diet Profiling Algorithm (DPA) to Rank Diet Quality Suitable to Implement in Digital Tools—A Test Study in a Cohort of Lactating Women

“…Previous results from our group have underlined the relevance of adequate leptin levels in breast milk for infant development [ 35 , 36 , 37 , 38 ]. Therefore, we tested the involvement of maternal diet quality on milk leptin and analyzed its relationship with the DPA score.…”

Maternal Supplementation with a Cocoa Extract during Lactation Deeply Modulates Dams’ Metabolism, Increases Adiponectin Circulating Levels and Improves the Inflammatory Profile in Obese Rat Offspring

“…First, polyphenols have been shown to induce epigenetic modifications including DNA methylation, histone acetylation and miRNAs regulation [ 86 ], which could explain these persistent metabolic effects in the adult age of the offspring. Interestingly, breast milk miRNAs related to adiponectin function have been described to be altered by maternal diet in rats [ 87 ]. Second, oxidative stress plays a crucial role in the developmental programming of MetS [ 88 ] and, thus, the metabolic programming effects associated to antioxidant molecules such as polyphenols can be explained by a reduction of oxidative stress in early life.…”