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Metabolic partitioning of oxidative metabolism in ketotic rat brain (643.2)
Author(s) -
Zhang Yifan,
Zhang Shenghui,
Xu Kui,
Puchowicz Michelle
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.643.2
Subject(s) - ketosis , ketone bodies , chemistry , citric acid cycle , medicine , endocrinology , glutamine , ketone , metabolism , carbohydrate metabolism , ketogenic diet , oxidative phosphorylation , biochemistry , amino acid , diabetes mellitus , organic chemistry , psychiatry , epilepsy
We have previously reported decreased cerebral metabolic rate of glucose in brain of diet‐induced ketotic rats which inversely correlated with blood ketone levels. These data suggest a “switch” in substrate utilization from glucose to ketone bodies. The metabolic effect of ketosis on brain intermediary metabolism remains to be explored. In this study we investigated the effects of chronic ketosis on partitioning of substrate oxidation. We characterized the 13 C fractional contribution of ketones and glucose into citric acid cycle (CAC), GABA and neuro‐amino acids in ketotic rat brain using infusions 13 C‐stable isotope tracers. Isoptopomer analysis, gas and liquid chromatography mass spectrometry were applied. Results: 13 C percent label contribution from ketone bodies increased 100 fold towards GABA, and 7.9 and 4 fold for glutamate and glutamine with ketosis compared to non‐ketotic rats. The data show chronic ketosis increases ketone body carbon entry towards GABA which is supplied via CAC, suggesting a possible mechanism of neuroprotection. Grant Funding Source : NIH R01 HL092933‐01, R21 NS062048‐01