Antenatal corticosteroid therapy modulates hepatic AMPK phosphorylation and maternal lipid metabolism in early lactating rats

Hecht, Fernanda Ballerini; Teixeira, Caio Jordão; Souza, Dailson Nogueira de; Mesquita, Filiphe de Paula Nunes; Sodré, Frhancielly Shirley; Veronesi, Vanessa Barbosa; Rocha, Deborah Fabiana da; Menezes, Yan Guida Dantas de; Pioli, Mariana Rodrigues; Bordin, Silvana; Cecatti, José Guilherme; Luz, Adriana Gomes; Anhê, Gabriel Forato

doi:10.1016/j.biopha.2021.112355

Cited by 3 publications

(1 citation statement)

References 31 publications

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“…Researches have linked exposure to adverse conditions in utero with an increased risk of metabolic syndrome, type 2 diabetes, and cardiovascular diseases in adulthood [ 31 , 32 ]. Dexamethasone treatment during pregnancy is a known adverse factor during pregnancy for fetuses and also affects maternal metabolism at the peripartum [ 9 , 10 , 33 , 34 ]. In this study, pregnant rats were treated with dexamethasone (0.2 and 0.8 mg/kg·d) during middle to late pregnancy to investigate the effects of PDE on metabolic syndrome and its developmental origins.…”

Section: Discussionmentioning

confidence: 99%

Dexamethasone exposure during pregnancy triggers metabolic syndrome in offspring via epigenetic alteration of IGF1

Xiao,

He,

Liu

et al. 2024

Cell Commun Signal

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Background Previous research has reported that prenatal exposure to dexamethasone (PDE) results in organ dysplasia and increased disease susceptibility in offspring. This study aimed to investigate the epigenetic mechanism of metabolic syndrome induced by PDE in offspring. Methods Pregnant Wistar rats were administered dexamethasone, and their offspring’s serum and liver tissues were analyzed. The hepatocyte differentiation model was established to unveil the molecular mechanism. Neonatal cord blood samples were collected to validate the phenomenon and mechanism. Results The findings demonstrated that PDE leads to insulin resistance and typical metabolic syndrome traits in adult offspring rats, which originated from fetal liver dysplasia. Additionally, PDE reduced serum corticosterone level and inhibited hepatic insulin-like growth factor 1 (IGF1) signaling in fetal rats. It further revealed that liver dysplasia and functional impairment induced by PDE persist after birth, driven by the continuous downregulation of serum corticosterone and hepatic IGF1 signaling. Both in vitro and in vivo experiments confirmed that low endogenous corticosterone reduces the histone 3 lysine 9 acetylation (H3K27ac) level of IGF1 and its expression by blocking glucocorticoid receptor α, special protein 1, and P300 into the nucleus, resulting in hepatocyte differentiation inhibition and liver dysplasia. Intriguingly, neonatal cord blood samples validated the link between reduced liver function in neonates induced by PDE and decreased serum cortisol and IGF1 levels. Conclusions This study demonstrated that low endogenous glucocorticoid level under PDE lead to liver dysplasia by downregulating the H3K27ac level of IGF1 and its expression, ultimately contributing to metabolic syndrome in adult offspring.

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Section: Discussionmentioning

confidence: 99%

Dexamethasone exposure during pregnancy triggers metabolic syndrome in offspring via epigenetic alteration of IGF1

Xiao,

He,

Liu

et al. 2024

Cell Commun Signal

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The adaptation of maternal energy metabolism to lactation and its underlying mechanisms

Anhê

Bordin

2022

Molecular and Cellular Endocrinology

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Proton Pump Inhibitor Pantoprazole Modulates Intestinal Microbiota and Induces TLR4 Signaling and Fibrosis in Mouse Liver

Assalin

Almeida

Guadagnini

et al. 2022

IJMS

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Proton pump inhibitors (PPIs) are one of the most prescribed drugs around the world. PPIs induce microbiota modulation such as obesity both in humans and in animal models. However, since PPIs can induce microbiota modulation despite the absence of a high-fat diet or weight gain, it is an interesting model to correlate microbiota modulation with the establishment of non-alcoholic fatty liver disease (NAFLD). We investigated the effect of pantoprazole treatment on TLR4 signaling and liver histology in C57BL/6J mice for 60 days, trying to correlate microbiota modulation with some aspects of liver injury. We performed glucose (GTT) and insulin (ITT) tolerance tests, serum lipopolysaccharide (LPS) dosage, liver histology, liver and intestine extraction for Western blot and qPCR. Fecal microbiota were investigated via metagenomics. Chronic treatment with pantoprazole induced microbiota modulation and impaired ileum barrier integrity, without an association with insulin resistance. Furthermore, increased circulating LPS and increased Toll-like receptor 4 (TLR4) and TGFβ downstream signaling may have an important role in the development of the observed liver microvesicular steatosis and fibrosis. Finally, this model of PPI-induced changes in microbiota might be useful to investigate liver microvesicular steatosis and fibrosis.

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Antenatal corticosteroid therapy modulates hepatic AMPK phosphorylation and maternal lipid metabolism in early lactating rats

Cited by 3 publications

References 31 publications

Dexamethasone exposure during pregnancy triggers metabolic syndrome in offspring via epigenetic alteration of IGF1

Dexamethasone exposure during pregnancy triggers metabolic syndrome in offspring via epigenetic alteration of IGF1

The adaptation of maternal energy metabolism to lactation and its underlying mechanisms

Proton Pump Inhibitor Pantoprazole Modulates Intestinal Microbiota and Induces TLR4 Signaling and Fibrosis in Mouse Liver

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