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Postnatal triglyceride accumulation is regulated by mineralocorticoid receptor activation under basal and stress conditions
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Aroclor 1254 disrupts liver glycogen metabolism and enhances acute stressor-mediated glycogenolysis in rainbow trout
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Salicylate Disrupts Interrenal Steroidogenesis and Brain Glucocorticoid Receptor Expression in Rainbow Trout
No full textCoordinated Action of Corticotropin-Releasing Hormone and Cortisol Shapes the Acute Stress-Induced Behavioural Response in Zebrafish
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Stable-isotope tracing reveals the role of corticosteroid receptors in driving cortisol-mediated central and peripheral glucose regulation in zebrafish
Get PDFRationaleCorticosteroids play a crucial role in the stress-induced metabolic adjustments, and this stress response is conserved across vertebrates. In teleosts, cortisol is the principal glucocorticoid and regulates metabolic processes predominantly through the activation of the glucocorticoid receptor (GR). In zebrafish (Danio rerio), we recently showed that both the GR and the mineralocorticoid receptor (MR) are essential for stressor perception and metabolic regulation, especially related to glucose production and target-tissue glucose uptake. Here, we tested the hypothesis that GR and MR have distinct roles in modulating the tissue-specific glucose metabolism in response to cortisol stimulation during stress in fish.MethodsThis was tested using GR knockout (nr3c1−/−) and either wild-type or MR knockout (nr3c2−/−) zebrafish treated with cortisol to mimic a chronic stress condition. Stable isotope-labeled glucose (U-13C-glucose) was injected intraperitoneally, and the labeled intermediates were assessed to investigate the fate of the glucose carbon in the serum, liver, and brain. The metabolites in these tissues were analyzed using LC-MS to investigate the 13C incorporation across the metabolic pathway at a systems level.ResultsChronic cortisol stimulation enhanced glucose breakdown and its utilization in the TCA cycle for energy production. The GR and MR activation led to distinct and complementary effects on glucose utilization and the generation of TCA intermediates in the brain and liver, suggesting a tissue-specific role for these receptors in energy substrate partitioning during stress in fish.ConclusionOverall, our results underscore the roles of GR and MR activation in elevating circulating energy substrates and facilitating tissue-level oxidative capacity and biomolecule synthesis from glucose metabolism in response to chronic cortisol stimulation in fish
Crhr1 and epinephrine utilize the central Ras-MAPK pathway in mediating the acute stress-related locomotor activity in zebrafish larvae
Get PDFIntroductionAlthough the Crh-Crhr1 system is the proximal trigger for the stressor-induced corticosteroid release, its role in initiating the fight-or-flight response to an acute stressor is unclear. We hypothesized that the Crh-Crhr1 system deploys the central Ras-Mapk (mitogen-activated protein kinase) pathway and rapidly increases the locomotor activity in zebrafish larvae.MethodsWe tested this using an acute stressor-induced hyperactivity model in larval zebrafish that is Crhr1-dependent, and a pharmacological inhibitor of Ras (BAY-293). ResultsThe larval hyperactivity response to stress disappeared after pretreatment with BAY-293. Acute CRH exposure stimulated the hyperactivity but at a lower magnitude than epinephrine; however, both responses were inhibited by BAY-293. Immunohistochemical localization revealed rapid phosphorylation of ERK1/2 in the pallium and hypothalamic regions after acute CRH and epinephrine treatment. The lack of Crhr1 (crhr1-/-) upregulated the a1-adrenoceptors (adra1ab and adra1ba) and abolished the epinephrine-induced, but not the forskolin-induced hyperactivity. The acute stressor also increased the transcript abundance of c-fos, commonly used as a marker of neuronal activation and plasticity. This immediate early gene response to stress was mimicked by epinephrine, but not Crh treatment, and was Ras-dependent. The acute stressor- or epinephrine-induced c-fos response was unaltered in larvae lacking a functional Crhr1.DiscussionThis study reveals the activation of the Ras-Mapk pathway by Crhr1 as a central mechanism modulating the acute stress-induced larval hyper-locomotor activity but not the c-fos response in zebrafish. Altogether, our results suggest a complementary but essential role for Crhr1 in facilitating the epinephrine-mediated fight-or-flight response but not the stress-habituation response
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