Contribution of brain glucose and ketone bodies to oxidative metabolism

Yifan Zhang, Youzhi Kuang, Joseph C. Lamanna, Michelle Puchowicz

Research output: Chapter in Book/Report/Conference proceedingConference contribution

10 Citations (Scopus)

Abstract

Ketone bodies are an alternative energy substrate to glucose in brain. Under conditions of oxidative stress, we hypothesize that ketosis stabilizes glucose metabolism by partitioning glucose away from oxidative metabolism towards ketone body oxidation. In this study we assessed oxidative metabolism in ketotic rat brain using stable isotope mass spectrometry analysis. The contribution of glucose and ketone bodies to oxidative metabolism was studied in cortical brain homogenates isolated from anesthetized ketotic rats. To induce chronic ketosis, rats were fed either a ketogenic (high-fat, carbohydrate restricted) or standard rodent chow for 3 weeks and then infused intravenously with tracers of [U-13C] glucose or [U-13C] acetoacetate for 60 min. The measured percent contribution of glucose or ketone bodies to oxidative metabolism was analyzed by measuring the 13C-label incorporation into acetyl-CoA. Using mass spectrometry (gas-chromatography; GC-MS, and liquid-chromatography; LCMS) and isotopomer analysis, the fractional amount of substrate oxidation was measured as the M + 2 enrichment (%) of acetyl-CoA relative to the achieved enrichment of the infused precursors, [U-13C]glucose or [U-13C] acetoacetate. Results: the percent contribution of glucose oxidation in cortical brain in rats fed the ketogenic diet was 71.2 ± 16.8 (mean% ± SD) compared to the standard chow, 89.0 ± 14.6. Acetoacetate oxidation was significantly higher with ketosis compared to standard chow, 41.7 ± 9.4 vs. 21.9 ± 10.6. These data confer the high oxidative capacity for glucose irrespective of ketotic or non-ketotic states. With ketosis induced by 3 weeks of diet, cortical brain utilizes twice as much acetoacetate compared to non-ketosis.

Original languageEnglish (US)
Title of host publicationOxygen Transport to Tissue XXXIV
EditorsWilliam J. Welch, Duane F. Bruley, Fredrik Palm, Harrison Harrison
Pages365-370
Number of pages6
DOIs
StatePublished - Jan 1 2013

Publication series

NameAdvances in Experimental Medicine and Biology
Volume765
ISSN (Print)0065-2598

Fingerprint

Ketone Bodies
Metabolism
Brain
Glucose
Ketosis
Rats
Oxidation
Acetyl Coenzyme A
Nutrition
Mass spectrometry
Ketogenic Diet
Oxidative stress
Liquid chromatography
Substrates
Liquid Chromatography
Isotopes
Gas chromatography
Gas Chromatography-Mass Spectrometry
Labels
Rodentia

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Zhang, Y., Kuang, Y., Lamanna, J. C., & Puchowicz, M. (2013). Contribution of brain glucose and ketone bodies to oxidative metabolism. In W. J. Welch, D. F. Bruley, F. Palm, & H. Harrison (Eds.), Oxygen Transport to Tissue XXXIV (pp. 365-370). (Advances in Experimental Medicine and Biology; Vol. 765). https://doi.org/10.1007/978-1-4614-4989-8-51

Contribution of brain glucose and ketone bodies to oxidative metabolism. / Zhang, Yifan; Kuang, Youzhi; Lamanna, Joseph C.; Puchowicz, Michelle.

Oxygen Transport to Tissue XXXIV. ed. / William J. Welch; Duane F. Bruley; Fredrik Palm; Harrison Harrison. 2013. p. 365-370 (Advances in Experimental Medicine and Biology; Vol. 765).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Zhang, Y, Kuang, Y, Lamanna, JC & Puchowicz, M 2013, Contribution of brain glucose and ketone bodies to oxidative metabolism. in WJ Welch, DF Bruley, F Palm & H Harrison (eds), Oxygen Transport to Tissue XXXIV. Advances in Experimental Medicine and Biology, vol. 765, pp. 365-370. https://doi.org/10.1007/978-1-4614-4989-8-51
Zhang Y, Kuang Y, Lamanna JC, Puchowicz M. Contribution of brain glucose and ketone bodies to oxidative metabolism. In Welch WJ, Bruley DF, Palm F, Harrison H, editors, Oxygen Transport to Tissue XXXIV. 2013. p. 365-370. (Advances in Experimental Medicine and Biology). https://doi.org/10.1007/978-1-4614-4989-8-51
Zhang, Yifan ; Kuang, Youzhi ; Lamanna, Joseph C. ; Puchowicz, Michelle. / Contribution of brain glucose and ketone bodies to oxidative metabolism. Oxygen Transport to Tissue XXXIV. editor / William J. Welch ; Duane F. Bruley ; Fredrik Palm ; Harrison Harrison. 2013. pp. 365-370 (Advances in Experimental Medicine and Biology).
@inproceedings{35e5c3e05fb8406a82981cb458b7739b,
title = "Contribution of brain glucose and ketone bodies to oxidative metabolism",
abstract = "Ketone bodies are an alternative energy substrate to glucose in brain. Under conditions of oxidative stress, we hypothesize that ketosis stabilizes glucose metabolism by partitioning glucose away from oxidative metabolism towards ketone body oxidation. In this study we assessed oxidative metabolism in ketotic rat brain using stable isotope mass spectrometry analysis. The contribution of glucose and ketone bodies to oxidative metabolism was studied in cortical brain homogenates isolated from anesthetized ketotic rats. To induce chronic ketosis, rats were fed either a ketogenic (high-fat, carbohydrate restricted) or standard rodent chow for 3 weeks and then infused intravenously with tracers of [U-13C] glucose or [U-13C] acetoacetate for 60 min. The measured percent contribution of glucose or ketone bodies to oxidative metabolism was analyzed by measuring the 13C-label incorporation into acetyl-CoA. Using mass spectrometry (gas-chromatography; GC-MS, and liquid-chromatography; LCMS) and isotopomer analysis, the fractional amount of substrate oxidation was measured as the M + 2 enrichment ({\%}) of acetyl-CoA relative to the achieved enrichment of the infused precursors, [U-13C]glucose or [U-13C] acetoacetate. Results: the percent contribution of glucose oxidation in cortical brain in rats fed the ketogenic diet was 71.2 ± 16.8 (mean{\%} ± SD) compared to the standard chow, 89.0 ± 14.6. Acetoacetate oxidation was significantly higher with ketosis compared to standard chow, 41.7 ± 9.4 vs. 21.9 ± 10.6. These data confer the high oxidative capacity for glucose irrespective of ketotic or non-ketotic states. With ketosis induced by 3 weeks of diet, cortical brain utilizes twice as much acetoacetate compared to non-ketosis.",
author = "Yifan Zhang and Youzhi Kuang and Lamanna, {Joseph C.} and Michelle Puchowicz",
year = "2013",
month = "1",
day = "1",
doi = "10.1007/978-1-4614-4989-8-51",
language = "English (US)",
isbn = "9781461447719",
series = "Advances in Experimental Medicine and Biology",
pages = "365--370",
editor = "Welch, {William J.} and Bruley, {Duane F.} and Fredrik Palm and Harrison Harrison",
booktitle = "Oxygen Transport to Tissue XXXIV",

}

TY - GEN

T1 - Contribution of brain glucose and ketone bodies to oxidative metabolism

AU - Zhang, Yifan

AU - Kuang, Youzhi

AU - Lamanna, Joseph C.

AU - Puchowicz, Michelle

PY - 2013/1/1

Y1 - 2013/1/1

N2 - Ketone bodies are an alternative energy substrate to glucose in brain. Under conditions of oxidative stress, we hypothesize that ketosis stabilizes glucose metabolism by partitioning glucose away from oxidative metabolism towards ketone body oxidation. In this study we assessed oxidative metabolism in ketotic rat brain using stable isotope mass spectrometry analysis. The contribution of glucose and ketone bodies to oxidative metabolism was studied in cortical brain homogenates isolated from anesthetized ketotic rats. To induce chronic ketosis, rats were fed either a ketogenic (high-fat, carbohydrate restricted) or standard rodent chow for 3 weeks and then infused intravenously with tracers of [U-13C] glucose or [U-13C] acetoacetate for 60 min. The measured percent contribution of glucose or ketone bodies to oxidative metabolism was analyzed by measuring the 13C-label incorporation into acetyl-CoA. Using mass spectrometry (gas-chromatography; GC-MS, and liquid-chromatography; LCMS) and isotopomer analysis, the fractional amount of substrate oxidation was measured as the M + 2 enrichment (%) of acetyl-CoA relative to the achieved enrichment of the infused precursors, [U-13C]glucose or [U-13C] acetoacetate. Results: the percent contribution of glucose oxidation in cortical brain in rats fed the ketogenic diet was 71.2 ± 16.8 (mean% ± SD) compared to the standard chow, 89.0 ± 14.6. Acetoacetate oxidation was significantly higher with ketosis compared to standard chow, 41.7 ± 9.4 vs. 21.9 ± 10.6. These data confer the high oxidative capacity for glucose irrespective of ketotic or non-ketotic states. With ketosis induced by 3 weeks of diet, cortical brain utilizes twice as much acetoacetate compared to non-ketosis.

AB - Ketone bodies are an alternative energy substrate to glucose in brain. Under conditions of oxidative stress, we hypothesize that ketosis stabilizes glucose metabolism by partitioning glucose away from oxidative metabolism towards ketone body oxidation. In this study we assessed oxidative metabolism in ketotic rat brain using stable isotope mass spectrometry analysis. The contribution of glucose and ketone bodies to oxidative metabolism was studied in cortical brain homogenates isolated from anesthetized ketotic rats. To induce chronic ketosis, rats were fed either a ketogenic (high-fat, carbohydrate restricted) or standard rodent chow for 3 weeks and then infused intravenously with tracers of [U-13C] glucose or [U-13C] acetoacetate for 60 min. The measured percent contribution of glucose or ketone bodies to oxidative metabolism was analyzed by measuring the 13C-label incorporation into acetyl-CoA. Using mass spectrometry (gas-chromatography; GC-MS, and liquid-chromatography; LCMS) and isotopomer analysis, the fractional amount of substrate oxidation was measured as the M + 2 enrichment (%) of acetyl-CoA relative to the achieved enrichment of the infused precursors, [U-13C]glucose or [U-13C] acetoacetate. Results: the percent contribution of glucose oxidation in cortical brain in rats fed the ketogenic diet was 71.2 ± 16.8 (mean% ± SD) compared to the standard chow, 89.0 ± 14.6. Acetoacetate oxidation was significantly higher with ketosis compared to standard chow, 41.7 ± 9.4 vs. 21.9 ± 10.6. These data confer the high oxidative capacity for glucose irrespective of ketotic or non-ketotic states. With ketosis induced by 3 weeks of diet, cortical brain utilizes twice as much acetoacetate compared to non-ketosis.

UR - http://www.scopus.com/inward/record.url?scp=84867525468&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84867525468&partnerID=8YFLogxK

U2 - 10.1007/978-1-4614-4989-8-51

DO - 10.1007/978-1-4614-4989-8-51

M3 - Conference contribution

SN - 9781461447719

T3 - Advances in Experimental Medicine and Biology

SP - 365

EP - 370

BT - Oxygen Transport to Tissue XXXIV

A2 - Welch, William J.

A2 - Bruley, Duane F.

A2 - Palm, Fredrik

A2 - Harrison, Harrison

ER -