Gestational fish oil supplementation in a high-fat diet induces sex-specific myokine changes in weanling offspring Juliana Woyames, Isabela De Lima Martins, Manuella Soares De Souza, Bruna Braga Saggioro, Cissa Bastos Ribeiro Da Silva, et al. Journal of Endocrinology, 2025 Previous research showed that a maternal high-fat (HF) diet during the perinatal period impairs skeletal muscle metabolism in offspring. Supplementing the HF diet with fish oil (FO), a source of n-3 polyunsaturated fatty acids, during gestation partially mitigates these adverse effects at weaning. This study investigated whether maternal HF diet, with or without FO supplementation during gestation, alters the expression of muscle-secreted molecules (myokines) in female and male offspring at weaning. Female Wistar rats were fed a control (9% lipids) or HF diet (29% lipids) for 8 weeks before mating and throughout gestation and lactation. A subset of HF-fed dams received a 3% FO-supplemented HF diet (HFFO) during gestation. In glycolytic extensor digitorum longus (EDL) muscle, FO tended to decrease Nmb (neuromedin B) mRNA in females and increased Erfe (myonectin) mRNA in males, compared to sex-matched HF groups. HFFO males also exhibited elevated expression of genes involved in fatty acid uptake and oxidation, suggesting enhanced lipid metabolism. However, FO did not reverse the HF-induced downregulation of Igf1r in EDL or Igf1 in the oxidative soleus muscle of male offspring, and muscle fiber size remained unchanged across groups. In the soleus muscle, FO increased Il6 mRNA in females, while in males, FO induced FNDC5 (the irisin precursor), accompanied by increased uncoupling protein-1 in subcutaneous white adipose tissue, suggesting increased thermogenic activity. Gestational FO supplementation induces sex- and muscle-specific alterations in myokine expression in weanling offspring exposed to a maternal HF diet, potentially shaping early muscle metabolism and contributing to sex-dependent metabolic programming.
Prenatal Exposure to Herbicide 2,4-Dichlorophenoxyacetic Acid (2,4D) Exacerbates Zika Virus Neurotoxicity In Vitro and In Vivo Raissa Rilo Christoff, Débora Santos da Silva, Rafael Ferreira Lima, Ana Luiza Meneguci Moreira Franco, Luiza Mendonça Higa, et al. Environmental Toxicology, 2025 Zika virus (ZIKV) infection during pregnancy can lead to a set of congenital malformations known as Congenital ZIKV syndrome (CZS), whose main feature is microcephaly. The geographic distribution of CZS in Brazil during the 2015–2017 outbreak was asymmetrical, with a higher prevalence in the Northeast and Central‐West regions of the country, despite the ubiquitous distribution of the vector Aedes aegypti, indicating that environmental factors could influence ZIKV vertical transmission and/or severity. Here we investigate the involvement of the most used agrochemicals in Brazil with CZS. First, we exposed human neuroblastoma SK‐N‐AS cells to the 15 frequently used agrochemical molecules or derivative metabolites able to cross the blood–brain barrier. We found that a derived metabolite from a widely used herbicide in the Central‐West region, 2,4‐dichlorophenoxyacetic acid (2,4D), exacerbates ZIKV neurotoxic effects in vitro. We validate this observation by demonstrating vertical transmission leading to microcephaly in the offspring of immunocompetent C57BL/6J mice exposed to water contaminated with 0.025 mg/L of 2,4D. Newborn mice whose dams were exposed to 2,4D and infected with ZIKV presented a smaller brain area and cortical plate size compared to the control. Also, embryos from animals facing the co‐insult of ZIKV and 2,4D exposition presented higher Caspase 3 positive cells in the cortex, fewer CTIP2+ neurons and proliferative cells at the ventricular zone, and a higher viral load. This phenotype is followed by placental alterations, such as vessel congestion, and apoptosis in the labyrinth and decidua. We also observed a mild spatial correlation between CZS prevalence and 2,4D use in Brazil's North and Central‐West regions, with R2 = 0.4 and 0.46, respectively. Our results suggest that 2,4D exposition facilitates maternal vertical transmission of ZIKV, exacerbating CZS, possibly contributing to the high prevalence of this syndrome in Brazil's Central‐West region compared to other regions.
Aging promotes an increase in mitochondrial fragmentation in astrocytes Ana Paula Bergamo Araujo, Gabriele Vargas, Lívia de Sá Hayashide, Isadora Matias, Cherley Borba Vieira Andrade, et al. Frontiers in Cellular Neuroscience, 2024 IntroductionBrain aging involves a complex interplay of cellular and molecular changes, including metabolic alterations and the accumulation of senescent cells. These changes frequently manifest as dysregulation in glucose metabolism and mitochondrial function, leading to reduced energy production, increased oxidative stress, and mitochondrial dysfunction—key contributors to age-related neurodegenerative diseases.MethodsWe conducted experiments on two models: young (3–4 months) and aged (over 18 months) mice, as well as cultures of senescent and control mouse astrocytes. Mitochondrial content and biogenesis were analyzed in astrocytes and neurons from aged and young animals. Cultured senescent astrocytes were examined for mitochondrial membrane potential and fragmentation. Quantitative PCR (qPCR) and immunocytochemistry were used to measure fusion- and fission-related protein levels. Additionally, transmission electron microscopy provided morphological data on mitochondria.ResultsAstrocytes and neurons from aged animals showed a significant reduction in mitochondrial content and a decrease in mitochondrial biogenesis. Senescent astrocytes in culture exhibited lower mitochondrial membrane potential and increased mitochondrial fragmentation. qPCR and immunocytochemistry analyses revealed a 68% increase in fusion-related proteins (mitofusin 1 and 2) and a 10-fold rise in DRP1, a key regulator of mitochondrial fission. Transmission electron microscopy showed reduced perimeter, area, and length-to-diameter ratio of mitochondria in astrocytes from aged mice, supported by elevated DRP1 phosphorylation in astrocytes of the cerebral cortex.DiscussionOur findings provide novel evidence of increased mitochondrial fragmentation in astrocytes from aged animals. This study sheds light on mechanisms of astrocytic metabolic dysfunction and mitochondrial dysregulation in brain aging, highlighting mitochondrial fragmentation as a potential target for therapeutic interventions in age-related neurodegenerative diseases.
Effect of Gestational Fish Oil Supplementation on Liver Metabolism and Mitochondria of Male and Female Rat Offspring Programmed by Maternal High-Fat Diet Jessika Geisebel Oliveira Neto, Juliana Woyames, Cherley Borba Vieira Andrade, Mariana Macedo de Almeida, Larissa Brito Fassarella, et al. Molecular Nutrition and Food Research, 2023 ScopePerinatal maternal moderately high‐fat diet (mHFD) is associated with obesity and fatty liver disease in offspring, and maternal fish oil (FO: n‐3 PUFA source) supplementation may attenuate these disorders. This study evaluates the effects of FO given to pregnant rats fed a mHFD on the offspring's liver at weaning.Methods and resultsFemale Wistar rats receive an isoenergetic, control (CT: 10.9% from fat) or high‐fat (HF: 28.7% from fat) diet before mating, and throughout pregnancy and lactation. FO supplementation (HFFO: 2.9% of FO in the HF diet) is given to one subgroup of HF dams during pregnancy. At weaning, male and female mHFD offspring display higher body mass, adiposity, and hepatic cellular damage, steatosis, and inflammation, accompanied by increased damaged mitochondria. FO does not protect pups from systemic metabolic alterations and partially mitigates hepatic histological damage induced by mHFD only in females. However, FO reduces mRNA expression of lipogenic genes, and mitochondrial damage, and modified mitochondrial morphology suggestive of early adaptations via mitochondrial dynamics.ConclusionsGestational FO supplementation has limited beneficial effects on the damage caused by perinatal mHFD consumption in offspring's liver at weaning. However, FO imprinting effect on lipid metabolism and mitochondria may have beneficial long‐term outcomes.
Cirrhotic Liver Sustains In Situ Regeneration of Acellular Liver Scaffolds after Transplantation into G-CSF-Treated Animals Marlon Lemos Dias, Inês Julia Ribas Wajsenzon, Gabriel Bastos Naves Alves, Bruno Andrade Paranhos, Cherley Borba Vieira Andrade, et al. Cells, 2023 Acellular liver scaffolds (ALS) produced by decellularization have been successfully explored for distinct regenerative purposes. To date, it is unknown whether transplanted ALSs are affected by cirrhotic livers, either becoming cirrhotic themselves or instead remaining as a robust template for healthy cell growth after transplantation into cirrhotic rats. Moreover, little is known about the clinical course of recipient cirrhotic livers after ALS transplantation. To address these questions, we transplanted ALSs into cirrhotic rats previously treated with the granulocyte colony-stimulating factor. Here, we report successful cellular engraftment within the transplanted ALSs at 7, 15, and 30 days after transplantation. Recellularization was orchestrated by liver tissue cell activation, resident hepatocytes and bile duct proliferation, and an immune response mediated by the granulocyte components. Furthermore, we showed that transplanted ALSs ensured a pro-regenerative and anti-inflammatory microenvironment, attracted vessels from the host cirrhotic tissue, and promoted progenitor cell recruitment. ALS transplantation induced cirrhotic liver regeneration and extracellular matrix remodeling. Moreover, the transplanted ALS sustained blood circulation and attenuated alterations in the ultrasonographic and biochemical parameters in cirrhotic rats. Taken together, our results confirm that transplanted ALSs are not affected by cirrhotic livers and remain a robust template for healthy cell growth and stimulated cirrhotic liver regeneration.
