γ-Linolenic acid in maternal milk drives cardiac metabolic maturation.

Birth presents a metabolic challenge to cardiomyocytes as they reshape fuel preference from glucose to fatty acids for postnatal energy production1,2. This adaptation is triggered in part by post-partum environmental changes3, but the molecules orchestrating cardiomyocyte maturation remain unknown. Here we show that this transition is coordinated by maternally supplied γ-linolenic acid (GLA), an 18:3 omega-6 fatty acid enriched in the maternal milk. GLA binds and activates retinoid X receptors4 (RXRs), ligand-regulated transcription factors that are expressed in cardiomyocytes from embryonic stages. Multifaceted genome-wide analysis revealed that the lack of RXR in embryonic cardiomyocytes caused an aberrant chromatin landscape that prevented the induction of an RXR-dependent gene expression signature controlling mitochondrial fatty acid homeostasis. The ensuing defective metabolic transition featured blunted mitochondrial lipid-derived energy production and enhanced glucose consumption, leading to perinatal cardiac dysfunction and death. Finally, GLA supplementation induced RXR-dependent expression of the mitochondrial fatty acid homeostasis signature in cardiomyocytes, both in vitro and in vivo. Thus, our study identifies the GLA-RXR axis as a key transcriptional regulatory mechanism underlying the maternal control of perinatal cardiac metabolism.

Mortality, hospitalizations, and persistence of symptoms in the outpatient setting of the first COVID-19 wave in Brazil: results of SARS-Brazil cohort study.

OBJECTIVE: To evaluate deaths, hospitalizations, and persistence of symptoms in patients with COVID-19 after infection in an outpatient setting during the first COVID-19 wave in Brazil. METHODS: This prospective cohort was between April 2020 and February 2021. Hospitalized or non-hospitalized COVID-19 patients until five days after symptom onset were included. The outcomes measured were incidence of death, hospitalization, and persistence of more than two symptoms 60 days after discharge. RESULTS: Out of 1,198 patients enrolled in the study, 66.7% were hospitalized. A total of 289 patients died (1 [0.3%] non-hospitalized and 288 [36%] hospitalized). At 60 days, patients non-hospitalized during admission had more persistent symptoms (16.2%) compared to hospitalized (37.1%). The COVID-19 severity variables associated with the persistence of two or more symptoms were increased age (OR= 1.03; p=0.015), respiratory rate at hospital admission (OR= 1.11; p=0.005), length of hospital stay of more than 60 days (OR= 12.24; p=0.026), and need for intensive care unit admission (OR= 2.04; p=0.038). CONCLUSION: COVID-19 survivors who were older, tachypneic at admission, had a hospital length of stay >60 days, and were admitted to the intensive care unit had more persistent symptoms than patients who did not require hospitalization in the early COVID-19 waves.ClinicalTrials.gov Identifier: NCT04479488.