Tissue-specific Short Chain Fatty Acid Metabolism and Slow Metabolic Recovery after Ischemia from Hyperpolarized NMR in Vivo

Pernille Rose Jensen, Torben Peitersen, Magnus Karlsson, Rene in't Zandt, Anna Gisselsson, Georg Hansson, Sebastian Meier, Mathilde Hauge Lerche

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Mechanistic details of mammalian metabolism in vivo and dynamic metabolic changes in intact organisms are difficult to monitor because of the lack of spatial, chemical, or temporal resolution when applying traditional analytical tools. These limitations can be addressed by sensitivity enhancement technology for fast in vivo NMR assays of enzymatic fluxes in tissues of interest. We apply this methodology to characterize organ-specific short chain fatty acid metabolism and the changes of carnitine and coenzyme A pools in ischemia reperfusion. This is achieved by assaying acetyl-CoA synthetase and acetyl-carnitine transferase catalyzed transformations in vivo. The fast and predominant flux of acetate and propionate signal into acyl-carnitine pools shows the efficient buffering of free CoA levels. Sizeable acetyl-carnitine formation from exogenous acetate is even found in liver, where acetyl-CoA synthetase and acetylcarnitine transferase activities have been assumed sequestered in different compartments. In vivo assays of altered acetate metabolism were applied to characterize pathological changes of acetate metabolism upon ischemia. Coenzyme pools in ischemic skeletal muscle are reduced in vivo even 1 h after disturbing muscle perfusion. Impaired mitochondrial metabolism and slow restoration of free CoA are corroborated by assays employing fumarate to show persistently reduced tricarboxylic acid (TCA) cycle activity upon ischemia. In the same animal model, anaerobic metabolism of pyruvate and tissue perfusion normalize faster than mitochondrial bioenergetics.
Original languageEnglish
JournalJournal of Biological Chemistry
Volume284
Issue number52
Pages (from-to)36077-36082
Number of pages6
ISSN0021-9258
DOIs
Publication statusPublished - 2009
Externally publishedYes

Keywords

  • Acetylcarnitine
  • Animals
  • Carnitine
  • Citric Acid Cycle
  • Coenzyme A
  • Coenzyme A Ligases
  • Energy Metabolism
  • Fatty Acids
  • Fumarates
  • Liver
  • Mice
  • Mitochondria, Liver
  • Mitochondria, Muscle
  • Muscle, Skeletal
  • Organ Specificity
  • Reperfusion Injury
  • 541-15-1 Carnitine
  • 6DH1W9VH8Q Acetylcarnitine
  • EC 6.2.1.- Coenzyme A Ligases
  • SAA04E81UX Coenzyme A
  • Acids
  • Biochemistry
  • Fatty acids
  • Lakes
  • Mammals
  • Muscle
  • Nuclear magnetic resonance
  • Metabolism
  • acetic acid
  • acetyl coenzyme A synthetase
  • acetylcarnitine
  • carnitine
  • carnitine acetyltransferase
  • coenzyme A
  • fumaric acid
  • propionic acid
  • pyruvic acid
  • short chain fatty acid
  • anaerobic metabolism
  • animal experiment
  • animal model
  • animal tissue
  • article
  • catalysis
  • citric acid cycle
  • controlled study
  • enzyme assay
  • fatty acid analysis
  • fatty acid metabolism
  • hyperpolarization
  • in vivo study
  • mitochondrial respiration
  • mouse
  • muscle ischemia
  • muscle perfusion
  • nonhuman
  • nuclear magnetic resonance
  • priority journal
  • reperfusion
  • sensitivity analysis
  • signal transduction
  • skeletal muscle
  • tissue specificity
  • Animalia
  • Mammalia
  • Acetate metabolism
  • Acetyl-CoA
  • Anaerobic metabolism
  • Analytical tool
  • Animal model
  • Hyperpolarized
  • In-vivo
  • Ischemia reperfusion
  • Metabolic changes
  • Mitochondrial bioenergetics
  • Mitochondrial metabolism
  • Pathological changes
  • Pyruvates
  • Sensitivity enhancements
  • Short-chain fatty acids
  • Skeletal muscle
  • Synthetases
  • Temporal resolution
  • Tissue perfusion
  • Tricarboxylic acids
  • BIOCHEMISTRY
  • C-13 MAGNETIC-RESONANCE
  • RAT SKELETAL-MUSCLE
  • COENZYME-A
  • CARNITINE ACETYLTRANSFERASE
  • PROSTATE-CANCER
  • ACETATE
  • OXIDATION
  • SPECTROSCOPY
  • REPERFUSION
  • HEARTS
  • Rodentia Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Mammals, Nonhuman Vertebrates, Nonhuman Mammals, Rodents, Vertebrates) - Muridae [86375] mouse common strain-C57BL/6
  • acetate 71-50-1 metabolism signaling
  • acetyl-carnitine transferase
  • acetyl-CoA synthetase 9012-31-1 EC 6.2.1.1
  • acyl-carnitine
  • coenzyme A 85-61-0
  • fumarate 142-42-7
  • propionate 72-03-7 signaling
  • pyruvate 57-60-3
  • short chain fatty acid metabolism tissue specificity
  • 10060, Biochemistry studies - General
  • 10066, Biochemistry studies - Lipids
  • 10510, Biophysics - Bioenergetics: electron transport and oxidative phosphorylation
  • 10802, Enzymes - General and comparative studies: coenzymes
  • 13002, Metabolism - General metabolism and metabolic pathways
  • 14004, Digestive system - Physiology and biochemistry
  • 14504, Cardiovascular system - Physiology and biochemistry
  • 14508, Cardiovascular system - Blood vessel pathology
  • 17504, Muscle - Physiology and biochemistry
  • Bioenergetics
  • Cardiovascular System
  • Methods and Techniques
  • ischemia-reperfusion injury Reperfusion Injury (MeSH) vascular disease, injury
  • enzyme catalysis
  • mitochondrial bioenergetics
  • slow metabolic recovery
  • TCA cycle
  • Biochemistry and Molecular Biophysics
  • Transport and Circulation
  • liver digestive system
  • skeletal muscle muscular system
  • hyperpolarized NMR laboratory techniques, spectrum analysis techniques

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