Comment: For the last decades, the importance of breastfeeding in the development of the newborn has been demonstrated at different evolutionary levels, from affective development to body development. Very recently, a new layer of this importance has been unveiled.
The cardiomyocyte in the embryonic phase uses mostly glucose and lactic acid to obtain energy. This preference changes after birth, and the new-born cardiomyocyte starts using fatty acids for its energy production, although the mechanism of this metabolic shift has been unknown. In a very recent, elegant, and comprehensive study, Ana Paredes, Mercedes Ricote and colleagues, have demonstrated that the γ-linolenic acid (GLA) supplied by the maternal milk is the responsible of the metabolic transition from glucose to fatty acid preference for energy production, which is essential for cardiomyocyte maturation. More specifically, authors identified the retinoid X receptors (RXRs)-GLA axis as the as a key transcriptional regulatory mechanism underlying the maternal control of perinatal cardiac metabolism.
The authors demonstrated that myocardial-specific RXRs have a cell-autonomous essential role in cardiac physiology but not morphogenesis, irrespective of the distinct RXR dimer states, using a knockout mice model. In fact, the lack of RXR in embryonic cardiomyocytes resulted in a defective metabolic transition leading to perinatal cardiac dysfunction and death within 48 hours. On the other hand, C57Bl6/J mice fed with milk from dams under a fat-free diet, showed a marked reduction of lipid metabolism-related genes. Contrarily, key metabolic genes involved in glycolysis, Krebs cycle or mitochondrial oxidative phosphorylation complexes remained unaltered in these pups. When dams were supplemented with GLA, an induction of RXR-dependent expression of the mitochondrial fatty acid homeostasis signature in the cardiomyocytes of pups was observed, both in vitro and in vivo.
GLA is not very abundant in nature, but it is produced in the body by the conversion of linoleic acid (an essential fatty acid) by delta6-desaturase. Linoleic acid can be obtained primarily from vegetable oils, nuts and seeds. Once again, the importance of an adequate feeding of the mother during lactation is demonstrated. Although the human relevance of the observed findings might be validated, it appears wise to advise pregnant women to consume a diet rich in linoleic acid, and also carefully check the contained levels of GLA in human formula milk, for the sake of cardiomyocyte maturation and cardiac health.
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