Roles and regulation of ketogenesis in cultured astroglia and neurons under hypoxia and hypoglycemia

Shinichi Takahashi, Takuya Iizumi, Kyoko Mashima, Takato Abe, Norihiro Suzuki

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44 Citations (Scopus)


Exogenous ketone bodies (KBs), acetoacetate (AA), and b-hydroxybutyrate (BHB) act as alternative energy substrates in neural cells under starvation. The present study examined the endogenous ketogenic capacity of astroglia under hypoxia with/without glucose and the possible roles of KBs in neuronal energy metabolism. Cultured neurons and astroglia were prepared from Sprague-Dawley rats. Palmitic acid (PAL) and L-carnitine (LC) were added to the assay medium. The 4- to 24-hr production of AA and BHB was measured using the cyclic thio-NADH method.14C-labeled acid-soluble products (KBs) and14CO2 produced from [1-14C]PAL were also measured. L-[U-14C]lactic acid ([14C]LAC), [1-14C]pyruvic acid ([14C]PYR), or b-[1-14C]hydroxybutyric acid ([14C]BHB) was used to compare the oxidative metabolism of the glycolysis end products with that of the KBs. Some cells were placed in a hypoxic chamber (1% O2). PAL and LC induced a higher production of KBs in astroglia than in neurons, while the CO2 production from PAL was less than 5% of the KB production in both astroglia and neurons. KB production in astroglia was augmented by the AMP-activated protein kinase activators, AICAR and metformin, as well as hypoxia with/without glucose. Neuronal KB production increased under hypoxia in the absence of PAL and LC. In neurons, [14C]LAC and [14C]PYR oxidation decreased after 24 hr of hypoxia, while [14C]BHB oxidation was preserved. Astroglia responds to ischemia in vitro by enhancing KB production, and astroglia-produced KBs derived from fatty acid might serve as a neuronal energy substrate for the tricarboxylic acid cycle instead of lactate, as pyruvate dehydrogenase is susceptible to ischemia.

Original languageEnglish
JournalASN neuro
Issue number5
Publication statusPublished - 2014 Jul 1
Externally publishedYes


  • AMP-activated protein kinase
  • Acetoacetate
  • B-hydroxybutyrate
  • Ketone bodies
  • Long-chain fatty acids
  • Palmitic acid

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology


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