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Metabolic Energy Balances in Ketotic Rat Brain

Zhang, Yifan

Abstract Details

2013, Doctor of Philosophy, Case Western Reserve University, Biomedical Engineering.
The brain normally uses glucose as its primary fuel, but is able to use ketone bodies as an alternative fuel during fasting, starvation, or feeding of high-fat, low-carb diets. Ketosis, as a physiological state, has been shown to be neuroprotective since the 1920s. The biochemical links between ketosis and neuroprotection has been of interest to clinicians and scientists. To investigate the metabolic mechanism, we hypothesized that 1) the total energy demand (glucose + ketone bodies) is constant during ketosis 2) in chronic ketosis, ketone bodies spare glucose from oxidative metabolism and shunts towards neurotransmitters. Using Positron Emission Tomography (PET) and 2-tissue compartment modeling, we show that the cerebral metabolic rate of glucose (CMRglc) decreases linearly (9% per 1mM blood ketone body increase) in rats with diet-induced ketosis. In another study, using Liquid Chromatography and Gas-Chromatography Mass Spectrometry (LC-MS, GC-MS), we applied carbon-13 (13C) isotopic flux analysis in ketotic rat brains with either [U13C]-glucose or [U13C]-acetoacetate intravenous infusions. The data show that ketosis reduced glucose carbon flux into the citric acid cycle and ¿-aminobutyric acid (GABA), whereas ketone body carbon flux increased in these pathways. In conclusion, ketone bodies partition and spare glucose oxidative metabolism in ketotic rat brain. This may lead to further understanding to neuroprotection from changes of metabolic energy balances.
Joseph LaManna, Ph.D (Advisor)
Xin Yu, Sc.D (Committee Chair)
Michelle Puchowicz, Ph.D (Committee Member)
Zhenghong Lee, Ph.D (Committee Member)
Gerald Saidel, Ph.D (Committee Member)
Kingman Strohl, M.D (Committee Member)
193 p.

Recommended Citations

Citations

  • Zhang, Y. (2013). Metabolic Energy Balances in Ketotic Rat Brain [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1370371336

    APA Style (7th edition)

  • Zhang, Yifan. Metabolic Energy Balances in Ketotic Rat Brain. 2013. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1370371336.

    MLA Style (8th edition)

  • Zhang, Yifan. "Metabolic Energy Balances in Ketotic Rat Brain." Doctoral dissertation, Case Western Reserve University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=case1370371336

    Chicago Manual of Style (17th edition)