This fatty acid makes the heart work properly after birth.

A study conducted by researchers at the National Center for Cardiovascular Research (CNIC) revealed that breast milk intake is the essential signal for the neonatal heart to metabolically mature after birth, allowing the heart to function properly and ensuring postnatal survival.

Breast milk intake is the signal for the neonatal heart to metabolically mature, according to this mouse study

Specifically, it is the omega-6 fatty acid gamma linolenic acid (GLA) from breast milk that is responsible for binding to the cellular protein Retinoid X Receptor (RXR).

RXR is a protein that acts as a nutritional sensor for lipids and vitamin A derivatives, altering gene expression and influencing important biological functions such as immunity, cell differentiation or metabolism.

GLA-RXR Union

Once the RXR detects maternal GLA, it triggers genetic programs that equip mitochondria, the cell’s powerhouses, with the necessary proteins to begin consuming lipids, the mature heart’s main source of energy.

Study results may have therapeutic implications in mitochondrial and metabolic dysfunctions

The results, published in the journal Naturecould have major therapeutic implications in cardiovascular pathologies where there are mitochondrial and metabolic dysfunctions, as well as diseases related to changes in maturational processes after birth, says Mercedes Ricote, head of the Nuclear Receptor Signaling Group at CNIC and leader of the study.

CNIC researchers

From left to right: CNIC researchers Vanessa Núñez, Jesús Vázquez, Emilio Camafeita, Ana Paredes, Pablo Hernansanz-Agustín, Mercedes Ricote, Fátima Sánchez Cabo and Fernando Martínez. /CNIC

Research has shown, in a mouse model, that both the absence of RXR in the heart and the lack of the omega-6 fatty acid GLA in breast milk prevent the mitochondria from producing energy properly, leading to severe heart failure which ultimately leads to death. 24-48 hours after birth.

Lack of the GLA acid in breast milk or the RXR protein in the heart (to which it binds) prevents the mitochondria from producing energy, leading to heart failure

At birth, the baby’s heart must rapidly begin to produce energy to start heartbeats in the extrauterine environment. For this, cardiomyocytes, contractile cells of the myocardium, need to activate mitochondria, ATP-generating organelles (adenosine triphosphate or adenosine triphosphate) that sustain the cell’s bioenergetic pathways. Although this process is essential for the organism’s survival, until now there was very little information about the signals that trigger the physiological adaptation of the heart after childbirth.

Maintain a correct heartbeat

“The need to maintain a constant, uninterrupted heartbeat means that the heart requires high energy inputs,” explains Ricote. “To meet their energy needs, heart cells have very tight control over the cellular pathways that produce energy. However, any imbalance in these bioenergetic mechanisms can lead to the appearance of serious cardiovascular pathologies”.

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For the researcher, the novelty of this work “also lies in the fact that it is the first time that it is demonstrated that, contrary to what was believed, the RXR plays an essential role in the cardiac muscle. This discovery represents a very important conceptual advance in the scientific field of nuclear receptors.”

This is the first time that it has been shown that, contrary to what was believed, the RXR protein plays an essential role in cardiac muscle.

Mercedes Ricote, CNIC researcher

The study proposes a very innovative angle to understand the postnatal adaptations that are triggered for the body to meet the needs of the extrauterine environment. “Birth is a physiological challenge for the newborn”, says Ana Paredes, lead author and researcher at CNIC.

Breast milk signal to cardiomyocytes

“With this work, we demonstrate that the ingestion of breast milk, in addition to its nutritional function, plays a signaling role, alerting cardiomyocytes that they must activate their metabolism, as maternal physiology no longer supports them”, he adds.

summary chart

Study summary infographic / CNIC

The results, emphasize the researchers, open up the possibility of modulating the activity of the RXR in cardiac cells through the use of specific drugs, some of them approved by the health authorities of the United States (FDA) for the treatment of some types of cancer. “Our work proposes the RXR as a potential therapeutic target in neonatal heart diseases and in systemic pathologies caused by metabolic failures”, concludes Ricote.

In any case, the authors point out that this study focused only on mice and that it remains to be investigated whether human milk GLA is equally essential for cardiac function or metabolic maturation in the newborn.

Reference:

Paredes, A. et al. “G-linolenic acid in breast milk drives cardiac metabolic maturation” Nature (2023)

The CNIC teams led by doctors José Antonio Enríquez, Fátima Sánchez-Cabo and Jesús Vázquez collaborated in this study. Additionally, national and international laboratories intervened: the National Biotechnology Center and the Margarita Salas Biological Research Center, both belonging to the Superior Council for Scientific Research (CNB-CSIC, CIB-CSIC); Complutense University of Madrid (UCM); University of Barcelona (UB); Institute of Functional Biology and Genomics/ University of Salamanca (IBFG/USAL); CEMBIO/CEU São Paulo; CIBER for Cardiovascular Diseases (CIBERCV) and Karolinska Institute (Sweden).

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