Astrocyte arachidonate and palmitate uptake and metabolism is differentially modulated by dibutyryl-cAMP treatment

Seeger, Drew R.; Murphy, Cameron C.; Murphy, Eric J.

doi:10.1016/j.plefa.2016.05.003

Cited by 2 publications

(1 citation statement)

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“…To test the protective effects of tibolone during metabolic inflammation in astrocytes we defined three different metabolic scenarios: (1) A "healthy" scenario, where the rate of palmitate uptake was set freely by the optimizer. This scenario emulates the normal conditions of astrocytes metabolism (Supplementary Data Sheet 1), without any inflammatory response (Seeger et al, 2016). (2) An "induced inflammation by palmitate" scenario, where the uptake rate of palmitate was forced to be stable in the mean of the half maximal inhibitory concentration (IC 50 ) value for all the objective functions included in Table 1.…”

Section: Metabolic Scenariosmentioning

confidence: 99%

Multiple Pathways Involved in Palmitic Acid-Induced Toxicity: A System Biology Approach

et al. 2020

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Inflammation is a complex biological response to injuries, metabolic disorders or infections. In the brain, astrocytes play an important role in the inflammatory processes during neurodegenerative diseases. Recent studies have shown that the increase of free saturated fatty acids such as palmitic acid produces a metabolic inflammatory response in astrocytes generally associated with damaging mechanisms such as oxidative stress, endoplasmic reticulum stress, and autophagic defects. In this aspect, the synthetic neurosteroid tibolone has shown to exert protective functions against inflammation in neuronal experimental models without the tumorigenic effects exerted by sexual hormones such as estradiol and progesterone. However, there is little information regarding the specific mechanisms of tibolone in astrocytes during inflammatory insults. In the present study, we performed a genome-scale metabolic reconstruction of astrocytes that was used to study astrocytic response during an inflammatory insult by palmitate through Flux Balance Analysis methods and data mining. In this aspect, we assessed the metabolic fluxes of human astrocytes under three different scenarios: healthy (normal conditions), induced inflammation by palmitate, and tibolone treatment under palmitate inflammation. Our results suggest that tibolone reduces the L-glutamate-mediated neurotoxicity in astrocytes through the modulation of several metabolic pathways involved in glutamate uptake. We also identified a set of reactions associated with the protective effects of tibolone, including the upregulation of taurine metabolism, gluconeogenesis, cPPAR and the modulation of calcium signaling pathways. In conclusion, the different scenarios studied in our model allowed us to identify several metabolic fluxes perturbed under an inflammatory response and the protective mechanisms exerted by tibolone.

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Section: Metabolic Scenariosmentioning

confidence: 99%