γ-Linolenic acid in maternal milk drives cardiac metabolic maturation

Paredes, Ana; Justo-Méndez, Raquel; Jiménez-Blasco, Daniel; Núñez, Vanessa; Calero, Inmaculada Muñoz; Villalba-Orero, María; Alegre-Martí, Andrea; Gradillas, Ana; Sant’Anna, Viviane Aparecida Rodrigues; Were, Felipe; Huang, Zhiqiang; Hernansanz-Agustín, Pablo; Contreras, Carmen; Martínez, Fernando; Camafeita, Emilio; Vázquez, Jesús; Ruíz-Cabello, Jesús; Area‐Gómez, Estela; Sánchez‐Cabo, Fátima; Treuter, Eckardt; Bolaños, Juan P.; Estébanez‐Perpiñá, Eva; Rupérez, Javier; Barbas, Coral; Enríquez, José Antonio; Ricote, Mercedes

doi:10.1038/s41586-023-06068-7

Cited by 38 publications

(22 citation statements)

References 84 publications

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“…The unsaturated fatty acid γ-linolenic acid drives cardiac metabolic maturation. 5 We did not observe an effect of linoleic acid supplementation on cardiomyocyte maturation. Moreover, potential benefits of LAD initiated after birth remain unknown.…”

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confidence: 53%

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Temporal Effects of Safflower Oil Diet-Based Linoleic Acid Supplementation on Barth Syndrome Cardiomyopathy

Zhu,

Pang,

Nguyen

et al. 2024

Circulation

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contrasting

confidence: 53%

“…The unsaturated fatty acid γ-linolenic acid drives cardiac metabolic maturation. 5 We did not observe an effect of linoleic acid supplementation on In this study, dietary LA supplementation was achieved by using safflower oil as an ingredient in rodent diet. Palm oil, which contains low LA, was used in control diets.…”

mentioning

confidence: 62%

Temporal Effects of Safflower Oil Diet-Based Linoleic Acid Supplementation on Barth Syndrome Cardiomyopathy

Zhu,

Pang,

Nguyen

et al. 2024

Circulation

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“…Retinoid X receptors expressed in cardiomyocytes transmit signals from maternal milk-derived fatty acids to enable mitochondrial maturation and induce metabolic adaptation in neonatal hearts. 33 The triggers of metabolic reprogramming collectively include the changes of blood oxygen, metabolic substrates, hemodynamic stress, hormone levels, and maternal milk. They might be acting synergistically to trigger metabolic reprogramming and cell cycle exit shortly after birth.…”

Section: How Is Metabolic Reprogramming Triggered Shortly After Birth?mentioning

confidence: 99%

Metabolic Reprogramming: A Byproduct or a Driver of Cardiomyocyte Proliferation?

Chen,

Wu,

Liu

et al. 2024

Circulation

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Defining mechanisms of cardiomyocyte proliferation should guide the understanding of endogenous cardiac regeneration and could lead to novel treatments for diseases such as myocardial infarction. In the neonatal heart, energy metabolic reprogramming (phenotypic alteration of glucose, fatty acid, and amino acid metabolism) parallels cell cycle arrest of cardiomyocytes. The metabolic reprogramming occurring shortly after birth is associated with alterations in blood oxygen levels, metabolic substrate availability, hemodynamic stress, and hormone release. In the adult heart, myocardial infarction causes metabolic reprogramming but these changes cannot stimulate sufficient cardiomyocyte proliferation to replace those lost by the ischemic injury. Some putative pro-proliferative interventions can induce the metabolic reprogramming. Recent data show that altering the metabolic enzymes PKM2 [pyruvate kinase 2], LDHA [lactate dehydrogenase A], PDK4 [pyruvate dehydrogenase kinase 4], SDH [succinate dehydrogenase], CPT1b [carnitine palmitoyl transferase 1b], or HMGCS2 [3-hydroxy-3-methylglutaryl-CoA synthase 2] is sufficient to partially reverse metabolic reprogramming and promotes adult cardiomyocyte proliferation. How metabolic reprogramming regulates cardiomyocyte proliferation is not clearly defined. The possible mechanisms involve biosynthetic pathways from the glycolysis shunts and the epigenetic regulation induced by metabolic intermediates. Metabolic manipulation could represent a new approach to stimulate cardiac regeneration; however, the efficacy of these manipulations requires optimization, and novel molecular targets need to be defined. In this review, we summarize the features, triggers, and molecular regulatory networks responsible for metabolic reprogramming and discuss the current understanding of metabolic reprogramming as a critical determinant of cardiomyocyte proliferation.

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“…The development of the cardiovascular system in newborns is influenced not only by the gestational environment, but also by the postnatal maternal diet. Indeed, maternal milk provides nutrients (e.g., γ-linolenic acid) required for the cardiac metabolic switch that is essential for cardiomyocyte (CM) maturation in neonatal mice (Paredes et al, 2023). Although prenatal maternal exposures and postnatal events are recognized to affect the cardiovascular system of the newborn later in life, it is less clear whether early parental stress experiences can have a similar impact on the cardiovascular system of the next generation.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A paternal cardiac lesion induces cardiac adaptation in offspring

Coppe,

Galardi-Castilla,

Sanz-Morejón

et al. 2024

Preprint

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BackgroundFollowing cardiac injury, whether the heart is permanently damaged or regenerating, distal organs are subjected to changes in physiological function. It remains largely unknown whether a cardiac lesion can affect gametes and transmit heritable changes to subsequent generations. Here, we report the influence of paternal cardiac injury on the following generation.MethodsWe studied the intergenerational influence of neonatal cardiac injury in the mouse, an animal model capable of regenerating the heart after early life injury. Neonatal male mice were subjected to ventricular cryoinjury, crossed at adulthood, and their sires were compared with litters derived from uninjured male mice. We used echocardiography, histology, and single nuclei RNA-sequencing to thoroughly characterize cardiac morphology, composition, function, and response to cardiac insult.ResultsWe show that paternal cardiac injury affects the heart morphology of offspring under physiological conditions. Furthermore, in response to the same injury, the F1 generation derived from injured fathers shows better systemic and cardiac recovery, with non-pathological left ventricular enlargement and improved cardiac function during the regenerative process. This is accompanied by the activation of the immune system healing program at 3 weeks post-injury, together with enhanced transcription of genes associated with physiological hypertrophy.ConclusionsThe memory of a paternal neonatal lesion can be transmitted to offspring and improve their recovery from a cardiac insult.

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γ-Linolenic acid in maternal milk drives cardiac metabolic maturation

Cited by 38 publications

References 84 publications

Temporal Effects of Safflower Oil Diet-Based Linoleic Acid Supplementation on Barth Syndrome Cardiomyopathy

Temporal Effects of Safflower Oil Diet-Based Linoleic Acid Supplementation on Barth Syndrome Cardiomyopathy

Metabolic Reprogramming: A Byproduct or a Driver of Cardiomyocyte Proliferation?

A paternal cardiac lesion induces cardiac adaptation in offspring

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